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\u0412 \u0440\u0430\u043c\u043a\u0438\u0442\u0435 \u043d\u0430 \u0432\u0441\u0435\u043a\u0438 \u043a\u043b\u0438\u043d\u0438\u0447\u0435\u043d \u0441\u043b\u0443\u0447\u0430\u0439 \u0441 \u043b\u0435\u0447\u0435\u0431\u043d\u0430 \u0446\u0435\u043b \u043c\u043e\u0433\u0430\u0442 \u0434\u0430 \u0431\u044a\u0434\u0430\u0442 \u043f\u0440\u0438\u043b\u0430\u0433\u0430\u043d\u0438 \u043c\u0435\u0442\u043e\u0434\u0438 \u043a\u0430\u0442\u043e \u0430\u043a\u0442\u0438\u0432\u043d\u043e \u043f\u0440\u043e\u0441\u043b\u0435\u0434\u044f\u0432\u0430\u043d\u0435, \u0445\u0438\u0440\u0443\u0440\u0433\u0438\u044f, \u0445\u043e\u0440\u043c\u043e\u043d\u0430\u043b\u043d\u0430 \u0442\u0435\u0440\u0430\u043f\u0438\u044f, \u0445\u0438\u043c\u0438\u043e\u0442\u0435\u0440\u0430\u043f\u0438\u044f, \u0432\u0430\u043a\u0441\u0438\u043d\u0430\u0446\u0438\u044f, \u043b\u0435\u0447\u0435\u043d\u0438\u0435 \u043d\u0430 \u043a\u043e\u0441\u0442\u0438\u0442\u0435 \u0441 \u0440\u0430\u0434\u0438\u0439-223, \u043f\u0440\u0438\u0446\u0435\u043b\u043d\u043e PSMA \u043b\u0435\u0447\u0435\u043d\u0438\u0435 \u0441 \u043b\u0443\u0442\u0435\u0446\u0438\u0439 -177.<\/p>\n

[\/et_pb_text][et_pb_accordion disabled_on=“on|on|on“ _builder_version=“4.4.8″ disabled=“on“][et_pb_accordion_item title=“TANI H\u0130ZMETLER\u0130 – GALYUM-68 PSMA PET\/BT“ open=“on“ open_toggle_text_color=“#0ca7c5″ _builder_version=“4.4.8″ toggle_font=“|700|||||||“ toggle_font_size=“18px“]<\/p>\n

Endikasyon<\/b><\/span><\/p>\n

Ga-68 PSMA PET\/BT; <\/span><\/p>\n

1) Y\u00fcksek riskli hastal\u0131kta cerrahi i\u015flem ya da radyoterapi planlamas\u0131 \u00f6ncesi primer evrelemede, <\/span><\/p>\n

2) Radikal prostatektomi sonras\u0131 devam eden PSA y\u00fcksekli\u011fi veya radikal prostatektomi\/radyoterapi sonras\u0131 geli\u015fen PSA n\u00fcks\u00fc olan hastalarda t\u00fcm\u00f6r dokusunu g\u00f6stermede,<\/span><\/p>\n

3) Tedaviye yan\u0131t\u0131n de\u011ferlendirilmesinde endikedir. <\/span><\/p>\n

Galyum-68 PSMA PET\/BT Nedir?<\/b><\/span><\/p>\n

Teranostik <\/b>t\u0131p d\u00fcnyas\u0131nda yeni geli\u015fmekte olan bir aland\u0131r. T\u00fcm\u00f6re \u00f6zg\u00fcl bir ila\u00e7 ile g\u00f6r\u00fcnt\u00fcleme yaparak saptanan t\u00fcm\u00f6r ve metastazlar\u0131n\u0131n, nereye gidece\u011fi-ne kadar gidece\u011fi ve hastal\u0131kl\u0131 dokuyu etkileme g\u00fcc\u00fc \u00f6nceden bilinen yine \u00f6zg\u00fcl bir ila\u00e7 ile tedavi edilebildi\u011fi bir yakla\u015f\u0131md\u0131r. Bu yakla\u015f\u0131m, geleneksel t\u0131ptan ki\u015fiye \u00f6zg\u00fc \u00e7a\u011fda\u015f t\u0131p uygulamalar\u0131na ge\u00e7i\u015f yap\u0131lmas\u0131n\u0131 sa\u011flamaktad\u0131r.<\/span><\/p>\n

Prostat kanserinde, bir yandan Ga-68 PSMA PET\/BT<\/b> ile prostat kanserine ait t\u00fcm\u00f6ral dokular y\u00fcksek duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fckte g\u00f6r\u00fcnt\u00fclenebilmekte, di\u011fer yandan Lu-177 PSMA<\/b> ile bu t\u00fcm\u00f6ral dokular\u0131n \u00f6zg\u00fcl ve hedefe y\u00f6nelik tedavisi yap\u0131labilmektedir. <\/span>Bu, teranostik uygulamalar i\u00e7in olduk\u00e7a ba\u015far\u0131l\u0131 ve yeni bir y\u00f6ntemdir. <\/span><\/p>\n

Metastatik prostat kanserinde standart g\u00f6r\u00fcnt\u00fcleme, geleneksel olarak MR, BT ve t\u00fcm v\u00fccut kemik sintigrafisi\/taramas\u0131n\u0131 i\u00e7ermektedir. Ancak bu g\u00f6r\u00fcnt\u00fcleme y\u00f6ntemlerinin duyarl\u0131l\u0131\u011f\u0131, \u00f6zellikle oligometastatik durumda ve d\u00fc\u015f\u00fck PSA seviyelerinde olduk\u00e7a d\u00fc\u015f\u00fckt\u00fcr. Standart g\u00f6r\u00fcnt\u00fclemeler i\u00e7in di\u011fer yandan \u00f6zg\u00fcll\u00fckte de s\u0131n\u0131rl\u0131l\u0131klar bulunmaktad\u0131r. \u00d6yle ki, BT’deki benign lenf d\u00fc\u011f\u00fcm\u00fc b\u00fcy\u00fcmeleri ya da kemik sintigrafisindeki benign kemik lezyonlar\u0131, metastaz y\u00f6n\u00fcnde hatal\u0131 de\u011ferlendirmelere neden olmaktad\u0131r. Bu s\u0131n\u0131rl\u0131l\u0131klar nedeniyle, prostat kanserli hastalar i\u00e7in yeni g\u00f6r\u00fcnt\u00fcleme modalitelerine ihtiya\u00e7 duyulmaktad\u0131r.<\/span><\/p>\n

Prostat spesifik membran antijeni (PSMA), prostat h\u00fccrelerinin h\u00fccre y\u00fczeyinde eksprese edilen bir transmembran proteindir ve PSMA’n\u0131n, artan h\u00fccre displazisi ile ekspresyonu da artt\u0131\u011f\u0131 bilinmektedir. Prostat kanseri i\u00e7in do\u011frulanm\u0131\u015f iyi bir hedef olan PSMA’ya ba\u011flanabilen bir\u00e7ok k\u00fc\u00e7\u00fck molek\u00fcl geli\u015ftirilmi\u015ftir. Bunlardan baz\u0131lar\u0131 da Galyum-68 ba\u015fta olmak \u00fczere radyoaktif elementler ile i\u015faretlenerek N\u00fckleer T\u0131p\u2019ta, \u00f6zellikle de PET\/BT g\u00f6r\u00fcnt\u00fclemesinde kullan\u0131lmaya ba\u015flanm\u0131\u015ft\u0131r. <\/span><\/p>\n

Mevcut bilimsel kan\u0131tlara bak\u0131ld\u0131\u011f\u0131nda, Ga-68 PSMA PET\/BT’nin klinik karar vermeyi \u00f6nemli \u00f6l\u00e7\u00fcde etkiledi\u011fi g\u00f6r\u00fclmektedir. Tabii ki bunda Ga-68 PSMA PET\/BT’nin alternatif tekniklere k\u0131yasla \u00fcst\u00fcn duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fck de\u011ferlerini sa\u011flayarak prostat kanserinde, k\u00fc\u00e7\u00fck hacimli metastazlar\u0131 erken ve do\u011fru saptaman\u0131n \u00f6nemi b\u00fcy\u00fckt\u00fcr. <\/b><\/span><\/p>\n

Galyum-68 PSMA PET\/BT T\u00fcm\u00f6r Oda\u011f\u0131n\u0131 Nas\u0131l G\u00f6sterir?<\/b><\/span><\/p>\n

Ga-68 PSMA PET\/BT, prostat kanserini, artm\u0131\u015f prostata \u00f6zg\u00fc membran antijeni (PSMA, glutamat karboksipeptidaz II) ekspresyonu varl\u0131\u011f\u0131yla g\u00f6r\u00fcnt\u00fcleyen noninvazif bir g\u00f6r\u00fcnt\u00fcleme y\u00f6ntemidir. PSMA, \u00f6zellikle t\u00fcm prostat dokusunda bulunan bir transmembran proteindir ve PSMA ekspresyonu en \u00e7ok prostat kanserinde olmak \u00fczere, farkl\u0131 malignitelerde g\u00f6r\u00fclmektedir. Prostat adenokarsinomlar\u0131n\u0131n neredeyse t\u00fcm primer ve metastatik lezyonlar\u0131 PSMA ekspresyonu g\u00f6stermektedir. \u0130mm\u00fcnohistokimyasal \u00e7al\u0131\u015fmalar, de-diferansiye, metastatik veya hormona diren\u00e7li hastal\u0131k durumunda PSMA ekspresyonunun artt\u0131\u011f\u0131n\u0131 ve ekspresyon seviyesinin hastal\u0131k i\u00e7in \u00f6nemli bir prognostik g\u00f6sterge oldu\u011funu g\u00f6stermi\u015ftir.<\/span><\/p>\n

68Ga, s\u0131kl\u0131kla Germanyum-68\/Galyum-68 jenerat\u00f6r sistemlerinden elde edilen, fiziksel yar\u0131 \u00f6mr\u00fc 67.63 dakika olan radyoaktif bir elementtir. PSMA-11, PSMA-617 ve PSMA-I&T gibi 68Ga ile kompleks yapan d\u00fc\u015f\u00fck molek\u00fcl a\u011f\u0131rl\u0131kl\u0131 PSMA ligandlar\u0131 PET\/BT g\u00f6r\u00fcnt\u00fclemesi i\u00e7in \u00f6zel haz\u0131rlanm\u0131\u015f olup, t\u00fcm bu radyoligandlar t\u00fcm\u00f6r dokusunu saptamada benzer \u00f6zelliklere sahiptir. <\/span><\/p>\n

Galyum-68 PSMA PET\/BT Kimlere Uygulan\u0131r?<\/b><\/span><\/p>\n

Varolan bilimsel veriler Ga-68 PSMA PET\/BT g\u00f6r\u00fcnt\u00fclemesini, \u00f6zellikle prostat k\u00f6kenli kanser odaklar\u0131n\u0131n belirlenmesi amac\u0131yla kullan\u0131m\u0131n\u0131 desteklemektedir. Bu y\u00f6ntemle; BT, MR ve kemik sintigrafisi gibi geleneksel g\u00f6r\u00fcnt\u00fcleme metotlar\u0131 ile saptanamam\u0131\u015f k\u00fc\u00e7\u00fck metastazlar bile g\u00f6r\u00fcnt\u00fclenebilmektedir.\u00a0Ga-68 PSMA PET\/BT ba\u015fl\u0131ca \u015fu ama\u00e7lar i\u00e7in kullan\u0131lmaktad\u0131r:\u201d<\/span><\/p>\n

Avrupa \u00dcroloji Derne\u011fi Perspektifi<\/b><\/span><\/p>\n

Prostat kanserinde Ga-68 PSMA PET\/BT g\u00f6r\u00fcnt\u00fclemesi, \u00e7ok d\u00fc\u015f\u00fck serum PSA seviyelerindeki biyokimyasal n\u00fcks\u00fcn belirlenmesi i\u00e7in, \u201cAvrupa \u00dcroloji Derne\u011fi Prostat Kanseri K\u0131lavuzu\u201d gibi, b\u00fcy\u00fck klinik k\u0131lavuzlarda yerini almaya ba\u015flam\u0131\u015ft\u0131r. <\/span><\/p>\n

Biyokimyasal n\u00fcks hastalar\u0131nda g\u00f6r\u00fcnt\u00fcleme; uzak metastazlar\u0131n saptanmas\u0131nda ve lokal n\u00fcks\u00fcn saptanmas\u0131 ve lokalizasyonunda rol oynama potansiyeline sahiptir. Biyokimyasal n\u00fcks varl\u0131\u011f\u0131nda, metastazlar\u0131n erken saptanmas\u0131, hem primer radyoterapi sonras\u0131 hem de radikal prostatektomi sonras\u0131 klinik olarak son derece \u00f6nemlidir. Primer radyoterapi sonras\u0131 lokal n\u00fcks i\u00e7in yap\u0131lacak kurtarma tedavileri \u00f6nemli morbiditeye neden olaca\u011f\u0131ndan, bu hastalarda yarars\u0131z kurtarma tedavilerinin olas\u0131 morbiditesinden ka\u00e7\u0131nmak i\u00e7in metastatik hastalar\u0131n m\u00fcmk\u00fcn olan en y\u00fcksek duyarl\u0131l\u0131kta saptanmas\u0131 gereklidir. Di\u011fer yandan, kemik taramas\u0131 ve MRI ile standart g\u00f6r\u00fcnt\u00fcleme, PSA’s\u0131 2 ng\/mL’nin alt\u0131nda olan radikal prostatektomili erkeklerde d\u00fc\u015f\u00fck lezyon saptama oran\u0131na sahiptir. Bununla birlikte, Ga-68 PSMA PET\/BT’nin radikal prostatektomi sonras\u0131 bu hasta grubunda da, rezid\u00fcel kanseri g\u00f6stererek kurtarma radyoterapisi planlamas\u0131na rehberlik edebilece\u011fi g\u00f6sterilmi\u015ftir. <\/span><\/p>\n

Kan\u0131tlar, Ga-68 PSMA PET\/BT’nin lenf nodu ve kemik metastazlar\u0131n\u0131 saptamada, klasik kemik sintigrafisi ve abdominopelvik BT’den \u00e7ok daha duyarl\u0131 oldu\u011funu g\u00f6stermektedir. <\/span><\/p>\n

Klinik olarak anlaml\u0131 PSA relaps\u0131<\/b>: Tedavi ba\u015far\u0131s\u0131zl\u0131\u011f\u0131n\u0131 tan\u0131mlayan PSA d\u00fczeyi, uygulanan primer tedaviye (radikal prostatektomi veya primer radyoterapi) ba\u011fl\u0131 olarak de\u011fi\u015fir. Radikal prostatektomiden sonra, metastaz\u0131 en iyi tahmin eden PSA e\u015fik de\u011feri > 0.4 ng\/mL’dir. Bununla birlikte, ultra duyarl\u0131 PSA testine eri\u015fim ile bu seviyenin \u00e7ok daha alt\u0131ndaki PSA art\u0131\u015flar\u0131 saptanabilmektedir. Primer radyoterapiden sonraki ba\u015far\u0131s\u0131zl\u0131\u011f\u0131n\u0131n tan\u0131m\u0131 ise tedavi sonras\u0131 (nadir) PSA de\u011ferinden ba\u011f\u0131ms\u0131z olarak, nadir PSA de\u011ferinden > 2 ng\/mL’den daha y\u00fcksek PSA art\u0131\u015f\u0131d\u0131r.<\/span><\/p>\n

Avrupa \u00dcroloji Derne\u011fi Prostat Kanseri K\u0131lavuzu\u2019na 2019’da eklenen de\u011fi\u015fiklikler sonras\u0131nda, \u201cbiyokimyasal n\u00fcks\u00fc olan hastalarda g\u00f6r\u00fcnt\u00fcleme talimatlar\u0131\u201d ba\u015fl\u0131\u011f\u0131 alt\u0131nda bulun PSMA PET\/BT endikasyonlar\u0131 \u015f\u00f6yledir:<\/span><\/p>\n\n\n\n\n\n
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Radikal prostatektomi sonras\u0131 devam eden PSA y\u00fcksekli\u011fi saptanan hastalarda<\/b><\/span><\/p>\n<\/td>\n

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Metastatik hastal\u0131\u011f\u0131 d\u0131\u015flamak i\u00e7in, devam eden PSA > 0.2 ng\/mL olan erkeklere <\/span>Ga-68 PSMA<\/span> PET\/BT taramas\u0131 yap\u0131n.<\/span><\/p>\n<\/td>\n<\/tr>\n

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Radikal prostatektomi sonras\u0131, prostat spesifik antijen (PSA) n\u00fcks saptatan hastalarda<\/b><\/span><\/p>\n<\/td>\n

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PSA seviyesi > 0,2 ng\/mL ise ve g\u00f6r\u00fcnt\u00fcleme sonu\u00e7lar\u0131, sonraki tedavi kararlar\u0131n\u0131 etkileyecekse Ga-68 PSMA PET\/BT yap\u0131n.<\/span><\/p>\n<\/td>\n<\/tr>\n

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Radyoterapi sonras\u0131 PSA n\u00fcks\u00fc olan hastalarda<\/b><\/span><\/p>\n<\/td>\n

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K\u00fcratif kurtarma tedavisi i\u00e7in uygun hastalarda Ga-68 PSMA PET\/BT yap\u0131n.<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n


EANM\/SNMMI Perspektifi<\/b><\/span><\/p>\n

Ga-68 PSMA PET\/BT’nin farkl\u0131 klinik durumlarda (tedavi \u00f6ncesi ilk evreleme, farkl\u0131 primer tedaviler sonras\u0131 yeniden evreleme, ilerlemi\u015f hastal\u0131k gibi), prostat kanserli hastalar\u0131n evrelenmesi ve y\u00f6netimi \u00fczerine etkilerine bak\u0131ld\u0131\u011f\u0131nda, Ga-68 PSMA PET\/BT \u00f6ncesi hekimi taraf\u0131ndan belirlenmi\u015f hastal\u0131k evresinin, olgular\u0131n %69’unda Ga-68 PSMA PET\/BT sonras\u0131 de\u011fi\u015fti\u011fi g\u00f6r\u00fclmektedir. Bu de\u011fi\u015fiklik %38 olguda \u201cupstaging\u201d, %30 olguda ise \u201cdownstaging\u201d \u015feklindedir. Bu de\u011fi\u015fim t\u00fcm klinik senaryolar i\u00e7in ge\u00e7erlidir ve beklendi\u011fi gibi, evreleme \u00fczerindeki en d\u00fc\u015f\u00fck etki, cerrahi sonras\u0131 serum PSA seviyeleri \u22640.2 ng\/mL olan olgularda saptanm\u0131\u015ft\u0131r (%31, t\u00fcm\u00fc de \u201cdownstaging\u201d). <\/span><\/p>\n

Ga-68 PSMA PET\/BT’nin, farkl\u0131 klinik durumdaki prostat kanseri hastalar\u0131n\u0131n tedavi yakla\u015f\u0131m\u0131 \u00fczerindeki etkisine bakt\u0131\u011f\u0131m\u0131zda ise olgular\u0131n %57’sinde tedavi yakla\u015f\u0131m\u0131nda de\u011fi\u015fikli\u011fe neden oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Olgularda en s\u0131k g\u00f6r\u00fclen de\u011fi\u015fim, sistemik tedaviden fokal tedaviye ge\u00e7i\u015f (%16) ve fokal tedavilerdeki de\u011fi\u015fiklik (%10) \u015feklinde olmu\u015ftur. <\/span><\/p>\n

N\u00fcks Prostat Kanserinde T\u00fcm\u00f6r Dokusunun G\u00f6sterilmesi<\/b><\/span><\/p>\n

N\u00fcks b\u00f6lgesini tan\u0131mlamak ve muhtemelen kurtarma tedavisine y\u00f6nlendirmek amac\u0131yla,\u00a0 <\/span>PSA de\u011feri 0,2 ile 10 ng\/mL aras\u0131nda olan hastalarda \u00f6nerilmektedir. Daha k\u0131sa PSA ikiye katlanma s\u00fcreleri (doubling time, PSADT) olan ve daha y\u00fcksek ba\u015flang\u0131\u00e7 Gleason skorlar\u0131 olan hastalarda ise Ga-68 PSMA PET\/BT ile daha y\u00fcksek duyarl\u0131l\u0131\u011fa ula\u015f\u0131lmaktad\u0131r. Art\u0131k bu d\u00fc\u015f\u00fck PSA seviyelerinde konvansiyonel g\u00f6r\u00fcnt\u00fclemenin (BT, MR, kemik sintigrafisi) olduk\u00e7a yarars\u0131z oldu\u011fu anlay\u0131\u015f\u0131na sahibiz.<\/span><\/p>\n

Radikal prostatektomi sonras\u0131 farkl\u0131 artm\u0131\u015f PSA seviyelerinde, Ga-68 PSMA PET\/BT’nin pozitiflik oranlar\u0131 \u015fu \u015fekilde \u00f6zetlenebilir.<\/span><\/p>\n\n\n\n\n\n\n\n\n
\n

PSA d\u00fczeyi (ng\/mL)<\/b><\/span><\/p>\n<\/td>\n

\n

Pozitif Ga-68 PSMA PET\/BT oran\u0131<\/b><\/span><\/p>\n<\/td>\n<\/tr>\n

\n

0 \u2013 0.19<\/span><\/p>\n<\/td>\n

\n

%33<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

0.2 \u2013 0.49 <\/span><\/span><\/p>\n<\/td>\n

\n

%42<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

0.5 \u2013 0.99 <\/span><\/span><\/p>\n<\/td>\n

\n

%59<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

1 \u2013 1.99<\/span><\/p>\n<\/td>\n

\n

%75<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

>2\u00a0 <\/span><\/span><\/span><\/p>\n<\/td>\n

\n

%95<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

<\/span><\/p>\n

<\/span><\/p>\n\n\n\n\n\n\n\n\n
\n

N\u00fcks yeri<\/b><\/span><\/p>\n<\/td>\n

\n

Pozitif Ga-68 PSMA PET\/BT oran\u0131 <\/span> <\/span><\/b><\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Prostat yata\u011f\u0131 <\/span><\/span><\/p>\n<\/td>\n

\n

%27<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Lenf nodu \u2013 pelvik <\/span><\/span><\/p>\n<\/td>\n

\n

%40<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Lenf nodu \u2013 ekstraprostatik<\/span><\/p>\n<\/td>\n

\n

%21<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Kemik <\/span> <\/span><\/span><\/p>\n<\/td>\n

\n

%30<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Distal organ <\/span><\/span><\/p>\n<\/td>\n

\n

%10<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

<\/span> <\/span> <\/span> <\/span> <\/span> <\/span> <\/span> <\/span> <\/span> <\/span> <\/span> <\/span> <\/span><\/span><\/p>\n

PSA ikiye katlanma s\u00fcreleri (PSADT) ile pozitif PET\/BT PSMA oranlar\u0131 aras\u0131nda da s\u0131k\u0131 bir korelasyon vard\u0131r. \u015e\u00f6yle ki:<\/span><\/p>\n

<\/span><\/p>\n\n\n\n\n\n
\n

PSADT<\/b><\/span><\/p>\n<\/td>\n

\n

Pozitif Ga-68 PSMA PET\/BT oran\u0131<\/b><\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Uzun <\/span>(>6 ay) <\/span><\/span><\/p>\n<\/td>\n

\n

%64 <\/span><\/span><\/p>\n<\/td>\n<\/tr>\n

\n

K\u0131sa\u00a0 <\/span><\/span>(<6ay) <\/span><\/span><\/p>\n<\/td>\n

\n

%92<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

<\/span><\/p>\n

Y\u00fcksek Riskli Hastal\u0131kta Cerrahi Prosed\u00fcr ya da Radyoterapi Planlamas\u0131 \u00d6ncesi Primer Evreleme Yap\u0131lmas\u0131<\/b><\/span><\/p>\n

Y\u00fcksek riskli hastal\u0131\u011f\u0131 olan hastalarda (Gleason skoru >7, PSA >20 ng\/mL, klinik evre T2c – 3a) lenf nodu ve kemik metastaz\u0131 olas\u0131l\u0131\u011f\u0131 artm\u0131\u015ft\u0131r.<\/span><\/p>\n

Bir\u00e7ok \u00e7al\u0131\u015fmada, primer evrelemede Ga-68 PSMA PET\/BT’nin, metastaz saptamada BT, MR veya kemik taramas\u0131na k\u0131yasla \u00fcst\u00fcn oldu\u011fu g\u00f6sterilmi\u015ftir. BT veya MR ile anatomik olarak saptanamam\u0131\u015f lenf nodu metastazlar\u0131n\u0131n saptanmas\u0131 da hasta y\u00f6netimini \u00f6nemli \u00f6l\u00e7\u00fcde etkileyebilmektedir. Ancak Ga-68 PSMA PET\/BT ile birlikte gelen geli\u015fmi\u015f duyarl\u0131l\u0131\u011f\u0131n genel sa\u011f kal\u0131m \u00fczerindeki etki hen\u00fcz yan\u0131t beklemektedir. Ayr\u0131ca \u00f6n veriler, Ga-68 PSMA PET\/BT’nin kemik metastazlar\u0131n\u0131 saptamada da daha do\u011fru sonu\u00e7lar verdi\u011fini\u00a0 <\/span>g\u00f6stermi\u015ftir. Bununla birlikte, lokal t\u00fcm\u00f6r\u00fcn tan\u0131mlanmas\u0131nda, Ga-68 PSMA PET\/BT pelvik MR’\u0131n yerini alamamaktad\u0131r. <\/span><\/p>\n

Yeni Klinik Endikasyonlar<\/b><\/span><\/p>\n

PSMA hedefli radyoligand (Lu-177 PSMA) tedavisi \u00f6ncesi ve tedavisi s\u0131ras\u0131nda evreleme (esas olarak metastatik kastrasyona diren\u00e7li prostat kanserinde) Lu-177 PSMA vb. hedefe y\u00f6nelik tedavi \u00f6ncesi g\u00f6r\u00fcnt\u00fcleme (\u00f6rn. Lu-177 PSMA), t\u00fcm\u00f6ral PSMA ekspresyonun varl\u0131\u011f\u0131n\u0131 ve yo\u011funlu\u011funu belirlemek i\u00e7in \u00e7ok \u00f6nemlidir. Hedef lezyonlardaki d\u00fc\u015f\u00fck PSMA ekspresyonu, radyoligand tedavisi i\u00e7in de kontrendikasyondur. Dikkat edilmesi gereken bir di\u011fer nokta da Ga-68 PSMA PET\/BT’nin prostat kanserli hastalar\u0131n yakla\u015f\u0131k %5’i kadar\u0131nda yanl\u0131\u015f negatif sonu\u00e7 verdi\u011fidir. Ayr\u0131ca, ileri d\u00f6nem metastatik kastrasyona diren\u00e7li prostat kanseri hastalar\u0131nda, metastazlar\u0131n (ba\u015fl\u0131ca karaci\u011ferde) PSMA ekspresyonunu kaybedebilece\u011fi de bildirilmi\u015ftir.<\/span><\/p>\n

\u00d6nceki Biyopsisi Negatif Ancak Prostat Kanseri \u015e\u00fcphesi Y\u00fcksek Hastalarda Biyopsiye K\u0131lavuzluk<\/b> <\/span><\/p>\n

\u0130lk veriler prostat kanseri \u015f\u00fcphesi y\u00fcksek olan hastalarda, Ga-68 PSMA PET\/BT’nin, tekrarlanan biyopsilere k\u0131lavuzluk etmede de\u011ferli olabilece\u011fini g\u00f6stermektedir. Bu durumda tercihen Ga-68 PSMA PET\/BT g\u00f6r\u00fcnt\u00fcleri multiparametrik MRI ile birle\u015ftirilmelidir.<\/span><\/p>\n

Metastatik Prostat Kanserinde Sistemik Tedaviye Yan\u0131t\u0131n De\u011ferlendirilmesi<\/b><\/span><\/p>\n

Tedaviye yan\u0131t\u0131n anatomik de\u011ferlendirilmesinde RECIST 1.1’in yeri, \u00f6l\u00e7\u00fclemeyen lenf nodu ve sklerotik kemik metastazlar\u0131n\u0131n y\u00fcksek prevalans\u0131 nedeniyle k\u0131s\u0131tl\u0131d\u0131r. Kemik taramas\u0131 ise tedavi sonras\u0131 geli\u015fen alevlenme (flare) fenomeni nedeniyle hatal\u0131 de\u011ferlendirmeye neden olabilmektedir. B\u00f6yle bir ortamda sistemik hastal\u0131\u011f\u0131n izlenmesi Ga-68 PSMA PET\/BT i\u00e7in potansiyel bir uygulama alan\u0131 haline gelebilir. Bununla birlikte, Ga-68 PSMA PET\/BT’nin \u015fu an i\u00e7in di\u011fer y\u00f6ntemlerin s\u0131n\u0131rlamalar\u0131n\u0131n \u00fcstesinden gelip gelmedi\u011fi ve daha \u00fcst\u00fcn oldu\u011fu hen\u00fcz kan\u0131tlanamam\u0131\u015ft\u0131r.<\/span><\/p>\n

PSMA PET\/BT Progresyon (PPP) Kriterleri<\/b> <\/span><\/p>\n\n\n\n\n\n\n
\n

Progresyon Kriterleri <\/span><\/b><\/span><\/p>\n<\/td>\n

\n

A\u00e7\u0131klama<\/b><\/span><\/p>\n<\/td>\n<\/tr>\n

\n

\u22652 yeni PSMA pozitif lezyon<\/span><\/p>\n<\/td>\n

\n

\u22652 yeni PSMA pozitif uzak lezyon saptanmas\u0131 <\/span><\/p>\n<\/td>\n<\/tr>\n

\n

1 yeni PSMA pozitif lezyon <\/span><\/span><\/p>\n<\/td>\n

\n

1 yeni PSMA pozitif lezyonun saptanmas\u0131 art\u0131 uyumlu klinik ve\/veya laboratuvar veri varl\u0131\u011f\u0131nda, Ga-68 PSMA PET\/BT sonras\u0131 3 ay i\u00e7inde biyopsi veya korelatif g\u00f6r\u00fcnt\u00fcleme ile konfirmasyon \u00f6nerilir, ancak \u015fart de\u011fil.\u00a0<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Yeni lezyon yok ancak boyut art\u0131yor<\/span><\/p>\n<\/td>\n

\n

Boyut veya PSMA tutulumunda \u226530 art\u0131\u015f\u0131n saptanmas\u0131 art\u0131 uyumlu klinik ve\/veya laboratuvar veri varl\u0131\u011f\u0131nda, Ga-68 PSMA PET\/BT sonras\u0131 3 ay i\u00e7inde biyopsi veya korelatif g\u00f6r\u00fcnt\u00fcleme ile konfirme edilmelidir.<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

<\/span><\/p>\n

Farkl\u0131 Tedaviler \u0130\u00e7in \u00d6zel \u00d6neriler<\/b><\/span><\/p>\n

Ga-68 PSMA<\/span> PET\/BT ile tedaviye yan\u0131t\u0131n de\u011ferlendirildi\u011fi durumlarda, kemoterapi i\u00e7in 4 hafta, radyoterapi i\u00e7in 8 hafta beklenilmesi \u00f6nerilir. Cerrahi sonras\u0131nda ise daha da uzun s\u00fcre beklemek gerekebilir. \u00d6nerilen bu zaman aral\u0131klar\u0131, prospektif verilerin olmamas\u0131na kar\u015f\u0131n s\u0131kl\u0131kla klinik rutinde uygulanmaktad\u0131r. Asl\u0131nda Ga-68 PSMA PET\/BT g\u00f6r\u00fcnt\u00fcleme i\u00e7in gerekli olan g\u00fcvenilir zaman aral\u0131\u011f\u0131 \u015fu an i\u00e7in bilinmemektedir.<\/span><\/p>\n

Hayvan deneyleri ve insan \u00e7al\u0131\u015fmalar\u0131nda g\u00f6r\u00fcld\u00fc\u011f\u00fc gibi ADT, yanl\u0131\u015f pozitif bulgulara yol a\u00e7abilecek a\u015f\u0131r\u0131 PSMA ekspresyonu ile sonu\u00e7lanabilmektedir. Ancak ADT di\u011fer yandan da ger\u00e7ek pozitif bulgular\u0131n say\u0131s\u0131n\u0131 art\u0131rabilmektedir. ADT ve AR-hedefli tedavilerin Ga-68 PSMA tutulumu \u00fczerindeki etkisi, tedavinin ba\u015flamas\u0131ndan hemen sonra \u00e7ok daha belirgindir. Bu nedenle, Ga-68 PSMA PET\/BT ile ADT yan\u0131t\u0131n\u0131n de\u011ferlendirilmesi, tedavinin ba\u015flamas\u0131ndan sonra en erken 4-8 hafta sonra yap\u0131lmal\u0131d\u0131r. <\/span><\/p>\n

PSMA tedavisi yan\u0131t\u0131n\u0131 de\u011ferlendirmek i\u00e7in Ga-68 PSMA PET\/BT kullan\u0131m\u0131 hakk\u0131nda s\u0131n\u0131rl\u0131 data mevcuttur (\u00f6rn.Lu-177 PSMA-617 ile). Bununla birlikte \u00f6n veriler PSMA PET\/BT Progresyon (PPP) kriterlerinin bu durumda da uygulanabilece\u011fini g\u00f6stermektedir.<\/span><\/p>\n

SGK Perspektifi<\/b><\/span><\/p>\n

Sosyal G\u00fcvenlik Kurumu (SGK) Sa\u011fl\u0131k Uygulama Tebli\u011fi (SUT) EK-2\/D-1’de, Ga-68 PSMA PET\/BT’in prostat kanserli hastalarda kullan\u0131m endikasyonu \u015fu \u015fekildedir:\u00a0<\/span><\/p>\n

<\/span><\/p>\n\n\n\n
\n

Evreleme<\/b><\/span><\/p>\n<\/td>\n

\n

Gleason skor 7 veya \u00fcst\u00fc olan ve di\u011fer g\u00f6r\u00fcnt\u00fcleme y\u00f6ntemlerinde (Kemik Sintigrafisi, BT, MR vb.) \u015f\u00fcpheli lezyon bulunmas\u0131 durumunda, sadece 3. basamak resmi sa\u011fl\u0131k hizmet sunucular\u0131nda* yap\u0131lmas\u0131 halinde \u00f6denir.<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

*\u00dc\u00e7\u00fcnc\u00fc basamak resmi sa\u011fl\u0131k kurumu; Sa\u011fl\u0131k Bakanl\u0131\u011f\u0131na ba\u011fl\u0131 e\u011fitim ve ara\u015ft\u0131rma hastaneleri ve \u00f6zel dal e\u011fitim ve ara\u015ft\u0131rma hastaneleri ile bu hastanelere ba\u011fl\u0131 semt poliklinikleri, \u00fcniversite hastaneleri ile bu hastanelere ba\u011fl\u0131 sa\u011fl\u0131k uygulama ve ara\u015ft\u0131rma merkezleri, enstit\u00fcler ve semt poliklinikleri.<\/span><\/p>\n

Galyum-68 PSMA PET\/BT G\u00fcvenli midir?<\/b><\/span><\/p>\n

Ga-68 PSMA bir kontrast madde de\u011fildir ve uygulama s\u0131ras\u0131nda herhangi bir yan etki (alerjik reaksiyonlar, deri d\u00f6k\u00fcnt\u00fcs\u00fc, k\u0131zar\u0131kl\u0131k, bulant\u0131, kusma vb.) beklenmemektedir. Bununla birlikte beraberinde damardan kontrast madde uyguland\u0131\u011f\u0131 \u00f6zel durumlarda, kontrast alerjisi ve di\u011fer yan etkiler a\u00e7\u0131s\u0131ndan dikkatli olunmal\u0131d\u0131r. <\/span><\/p>\n

Ga-68, sadece 68 dakika gibi \u00e7ok k\u0131sa bir yar\u0131 \u00f6mre sahiptir ve ila\u00e7 uyguland\u0131ktan en ge\u00e7 6 saat sonra, v\u00fccuttaki radyasyon do\u011fal seviyeye geri d\u00f6nmektedir. Bu nedenle, ila\u00e7 verilmesini takiben ilk 6 saat k\u00fc\u00e7\u00fck \u00e7ocuklarla ve hamile kad\u0131nlarla temastan ka\u00e7\u0131n\u0131lmas\u0131 gerekir. <\/span><\/p>\n

Ga-68 PSMA PET\/BT i\u015flemi sonucu al\u0131nacak radyasyon dozu yakla\u015f\u0131k 5mSv’tir ve bu doz, bilgisayarl\u0131 tomografi gibi geleneksel bir tetkik sonucu al\u0131nacak doz ile ayn\u0131 d\u00fczeydedir.<\/span><\/p>\n

Galyum-68 PSMA PET\/BT \u00d6ncesi Haz\u0131rl\u0131k<\/b><\/span><\/p>\n

Ga-68 PSMA PET\/BT Tetkik \u0130stemi <\/b><\/span><\/p>\n

Ga-68 PSMA PET\/BT tetkik istemi; hastan\u0131n tan\u0131, risk grubu ve onkolojik ge\u00e7mi\u015fini kapsayan k\u0131sa bir \u00f6zeti de i\u00e7ermelidir.\u00a0<\/span><\/p>\n

Hasta dosyas\u0131 incelenmesinde dikkate al\u0131nacak hususlar \u015f\u00f6yledir:<\/span><\/p>\n

    \n
  • <\/span>G\u00f6r\u00fcnt\u00fcleme endikasyonu<\/span><\/li>\n
  • <\/span>Prostat kanserine \u00f6zg\u00fc \u00f6yk\u00fc:<\/span><\/li>\n<\/ul>\n

    a. Primer kanser<\/span><\/p>\n

    -PSA ve Gleason skoru<\/span><\/p>\n

    b. Biyokimyasal n\u00fcks <\/span><\/p>\n

    -PSA ve PSA kineti\u011fi<\/span><\/p>\n

    -\u00d6nceki tedaviler (\u00f6rn. prostatektomi, radyoterapi)<\/span><\/p>\n

    c. G\u00fcncel prostat kanseri ila\u00e7 tedavileri: Androjen deprivasyon tedavisi (ADT, antiandrojen tedavi, kastrasyon tedavisi) veya di\u011fer androjen resept\u00f6r\u00fc hedefli tedaviler. Yak\u0131n ge\u00e7mi\u015fte kemoterapi, Radyum-223 veya PSMA hedefli radyoligand tedavisi \u00f6yk\u00fcs\u00fc.<\/span><\/p>\n

    d. Hastal\u0131kla ili\u015fkili semptomlar (kemik a\u011fr\u0131s\u0131, s\u0131k idrara \u00e7\u0131kma, nokt\u00fcri, hemat\u00fcri, diz\u00fcri, iktidars\u0131zl\u0131k, erektil disfonksiyon veya a\u011fr\u0131l\u0131 bo\u015falma)<\/span><\/p>\n

    \u00a0\u00a0 \u00a0 \u00a0 <\/span><\/span>e. \u00d6nceki g\u00f6r\u00fcnt\u00fcleme bulgular\u0131<\/span><\/p>\n

      \n
    • <\/span>Hastal\u0131k ile ili\u015fkili komorbiditeler<\/span><\/li>\n<\/ul>\n

      \u00a0 \u00a0 \u00a0 \u00a0 <\/span><\/span>a. Prostat d\u0131\u015f\u0131 maligniteler<\/span><\/p>\n

      \u00a0 \u00a0 \u00a0 <\/span><\/span>b. Alerjiler<\/span><\/p>\n

      \u00a0 \u00a0 \u00a0 \u00a0 <\/span><\/span>c. B\u00f6brek yetmezli\u011fi<\/span><\/p>\n

      Hasta Haz\u0131rl\u0131\u011f\u0131<\/b><\/span><\/p>\n

      Hastalar\u0131n i\u015flem i\u00e7in a\u00e7 olmas\u0131 gerekmez ve t\u00fcm ila\u00e7lar\u0131n\u0131 kullanabilirler. Preklinik veriler, kastrasyona diren\u00e7li prostat kanserinde ve ADT alt\u0131nda PSMA ekspresyonunun artt\u0131\u011f\u0131n\u0131 g\u00f6stermektedir. Bununla birlikte, ADT’nin Ga-68 PSMA PET\/BT performans\u0131 \u00fczerindeki klinik etkisini de\u011ferlendirebilmek i\u00e7in daha fazla veriye ihtiya\u00e7 vard\u0131r. Hastalar g\u00f6r\u00fcnt\u00fclemeden \u00f6nce iyi hidrasyon yap\u0131lmal\u0131d\u0131r, bunun i\u00e7in g\u00f6r\u00fcnt\u00fclemeden 2 saat \u00f6nce 500 mL su oral al\u0131m\u0131 yeterli olacakt\u0131r. G\u00f6r\u00fcnt\u00fclemeden hemen \u00f6nce i\u015femeyle mesanenin bo\u015falt\u0131lmas\u0131 gerekmektedir. Buna ra\u011fmen, baz\u0131 durumlarda, \u00fcriner sistemde y\u00fcksek aktivite kalmakta ve PET\/BT\u2019de \u201chalo artefakt\u0131na\u201d yol a\u00e7abilmektedir. \u00dcreterlerdeki aktivite yanl\u0131\u015f pozitif bulgulara yol a\u00e7abilir. Bu durumda Furosemid uygulamas\u0131 (20 mg, i.v, Ga-68 PSMA’n\u0131n i.v. uygulanmas\u0131ndan hemen \u00f6nce ya da sonra) \u00f6zellikle yararl\u0131 olabilir.<\/span><\/p>\n

      Galyum-68 PSMA PET\/BT Nas\u0131l Uygulan\u0131r?<\/b><\/span><\/p>\n

      PET\/BT g\u00f6r\u00fcnt\u00fclemesi, Ga-68 PSMA’n\u0131n 1.8-2.2 Mbq\/Kg (0.049 \u2013 0.060 mCi\/Kg) dozunda i.v. bolus enjeksiyonu sonras\u0131 yakla\u015f\u0131k 60. dakikada yap\u0131l\u0131r. Birinci saat g\u00f6r\u00fcnt\u00fclemede arada kal\u0131nan olgularda, 3. saate kadar ge\u00e7 g\u00f6r\u00fcnt\u00fc al\u0131nmas\u0131 \u00fcretere veya mesaneye yak\u0131n lezyonlar\u0131n tan\u0131mlanmas\u0131nda veya d\u00fc\u015f\u00fck PSMA ekspresyonu g\u00f6steren lezyonlarda yard\u0131mc\u0131 olabilir.<\/span><\/p>\n

      Ga-68 PSMA PET\/BT- g\u00f6r\u00fcnt\u00fc elde etme ve rekonstr\u00fcksiyon i\u00e7in protokol \u00f6rne\u011fi<\/b><\/span>:<\/span><\/p>\n\n\n\n\n\n\n\n\n\n
      \n

      Hasta haz\u0131rl\u0131\u011f\u0131\u00a0 <\/span><\/span><\/span><\/p>\n<\/td>\n

      		\n

      G\u00f6r\u00fcnt\u00fclemeden 2 saat \u00f6nce 500 mL su oral al\u0131m\u0131 <\/span><\/span><\/p>\n<\/td>\n<\/tr>\n

      \n

      Aktivite\/Uygulama <\/span><\/span><\/p>\n<\/td>\n

      		\n

      1.8-2.2 Mbq\/Kg, i.v., ard\u0131ndan serum fizyolojik ile y\u0131ka<\/span><\/p>\n<\/td>\n<\/tr>\n

      \n

      E\u015fzamanl\u0131 ila\u00e7 <\/span> <\/span><\/span><\/p>\n<\/td>\n

      		\n

      Furosemid (20 mg, i.v.)<\/span><\/p>\n<\/td>\n<\/tr>\n

      \n

      Uptake (tutulum) zaman\u0131<\/span><\/p>\n<\/td>\n

      		\n

      60 dakika (kabul edilebilir aral\u0131k: 50 ila 100 dakika)<\/span><\/p>\n<\/td>\n<\/tr>\n

      \n

      Hasta pozisyonu <\/span><\/span><\/p>\n<\/td>\n

      		\n

      Kollar ba\u015f \u00fcst\u00fcnde, s\u0131rt \u00fcst\u00fc uzanarak<\/span><\/p>\n<\/td>\n<\/tr>\n

      \n

      BT Protokol\u00fc <\/span><\/span><\/p>\n<\/td>\n

      		\n

      FOV: kafa taban\u0131ndan uyluk ortas\u0131na kadar; <\/span><\/p>\n

      Faz: portal ven\u00f6z (kontrast maddeden 80 saniye sonra, 1.5 mL\/Kg<\/span><\/p>\n<\/td>\n<\/tr>\n

      \n

      PET\/BT Protokol\u00fc<\/span><\/p>\n<\/td>\n

      		\n

      FOV: uyluk ortas\u0131ndan kafa taban\u0131na kadar, yatak pozisyonu ba\u015f\u0131na 3-4 dk.<\/span><\/p>\n

      <\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n


      Raporlama<\/b><\/span><\/p>\n

      PSMA Tutulum Yeri, Yayg\u0131nl\u0131\u011f\u0131 ve Yo\u011funlu\u011funun Tan\u0131mlanmas\u0131<\/b><\/span><\/p>\n

      Genel g\u00f6zden ge\u00e7irmede, prostat bezi\/yata\u011f\u0131, seminal vezik\u00fcller, b\u00f6lgesel ve uzak lenf d\u00fc\u011f\u00fcmleri, kemikler, akci\u011ferler ve karaci\u011fere \u00f6ncelikle dikkat edilmelidir. \u0130stem formunda yer alan semptomlarla ili\u015fkili olabilecek b\u00f6lgelere de \u00f6zel dikkat g\u00f6sterilmelidir. Yar\u0131 kantitatif de\u011ferlere (maksimum SUV) ek olarak, lezyonlar\u0131n Ga-68 PSMA tutulum d\u00fczeyleri; arka plan tutulumla k\u0131yaslanarak, d\u00fc\u015f\u00fck, orta veya yo\u011fun olarak bildirilir. T\u00fcm\u00f6ral lezyonlar genellikle kom\u015fu arka plandan daha y\u00fcksek Ga-68 PSMA tutulumu g\u00f6sterirler. Ga-68 PSMA tutulumunun saptanabildi\u011fi her b\u00f6lge i\u00e7in, BT’de kar\u015f\u0131l\u0131k geldi\u011fi lezyon da rapor edilmelidir.<\/span><\/p>\n

      Normal Tutulum Ve \u00d6nemli Tuzaklar<\/b><\/span><\/p>\n

      A\u015fa\u011f\u0131daki dokularda normal ve de\u011fi\u015fken d\u00fczeylerde PSMA tutulumu g\u00f6r\u00fclebilmektedir:<\/span><\/p>\n

        \n
      • Fizyolojik<\/span><\/li>\n
      • G\u00f6zya\u015f\u0131 bezleri<\/span><\/li>\n
      • T\u00fck\u00fcr\u00fck bezleri<\/span><\/li>\n
      • Karaci\u011fer<\/span><\/li>\n
      • Dalak; splenosis ve aksesuar dalak dahil<\/span><\/li>\n
      • \u0130nce ba\u011f\u0131rsak ve kolon <\/span><\/li>\n
      • B\u00f6brekler<\/span><\/li>\n
      • Otonom sinir sistemi ganglionlar\u0131, en s\u0131k lomber olmak \u00fczere servikal, stellat, \u00e7\u00f6lyak ve sakral ganglionlar<\/span><\/li>\n
      • Radyoligand\u0131n \u00fcriner sistemden ekskresyonu, \u00fcreter, mesane <\/span><\/li>\n
      • Benign patolojiler<\/span><\/li>\n
      • Gran\u00fclomat\u00f6z hastal\u0131klar; sarkoidoz, Wegener gran\u00fclomatozu, t\u00fcberk\u00fcloz, antrakoslikozis<\/span><\/li>\n
      • Benign kemik hastal\u0131klar\u0131; fibr\u00f6z displazi, iyile\u015fen k\u0131r\u0131k, Paget hastal\u0131\u011f\u0131<\/span><\/li>\n
      • Benign n\u00f6rojenik t\u00fcm\u00f6rler; schwannoma ve di\u011fer periferik sinir k\u0131l\u0131f\u0131 t\u00fcm\u00f6rleri, meningioma<\/span><\/li>\n
      • Benign yumu\u015fak doku patolojileri; jinekomasti, hemanjioma, desmoid t\u00fcm\u00f6r, intramusk\u00fcler miksoma, ps\u00f6doanjiomat\u00f6z stromal hiperplazi<\/span><\/li>\n
      • Malign t\u00fcm\u00f6rler<\/span><\/li>\n
      • Multiple myelom<\/span><\/li>\n
      • Tiroid kanseri; med\u00fcller, papiller, folik\u00fcler<\/span><\/li>\n
      • Meme kanseri<\/span><\/li>\n
      • Akci\u011fer kanseri<\/span><\/li>\n
      • Pankreatik NET<\/span><\/li>\n
      • Renal h\u00fccreli karsinoma, metastatik<\/span><\/li>\n
      • Hepatosell\u00fcler karsinom<\/span><\/li>\n
      • Glioblastoma multiforme <\/span><\/li>\n<\/ul>\n

        Ga-68 PSMA ligandlar\u0131 \u00f6ncelikle \u00fcriner sistem yoluyla at\u0131l\u0131r ve mesanede toplan\u0131r,\u00a0 <\/span>hepatobiliyer sistem yoluyla ise k\u00fc\u00e7\u00fck bir oran temizlenir. Bu nedenle, idrar kesesi kom\u015fulu\u011fundaki, yumu\u015fak doku yap\u0131lar\u0131nda Ga-68 PSMA ligand al\u0131m\u0131n\u0131 de\u011ferlendirmek i\u00e7in SUV e\u015fi\u011finin do\u011fru ayarlanmas\u0131, k\u00fc\u00e7\u00fck lokal n\u00fcksleri atlamamak i\u00e7in \u00f6nemlidir. Normal salin inf\u00fczyonu ve\/veya furosemid uygulamas\u0131ndan sonra pelvise y\u00f6nelik ge\u00e7 g\u00f6r\u00fcnt\u00fcleme yap\u0131lmas\u0131 bu gibi durumlarda faydal\u0131 olabilir. Karaci\u011ferdeki y\u00fcksek arka plan aktivitesi nedeniyle, potansiyel karaci\u011fer metastazlar\u0131 saptanamayabilir. Bu durum, ileri metastatik hastal\u0131kta, karaci\u011fer metastazlar\u0131n\u0131n PSMA ekspresyonunu kaybetme e\u011filiminde olmas\u0131yla daha da belirginle\u015fir. Bu nedenle, ileri d\u00f6nem hastal\u0131kta, PET\/BT’nin BT komponenti, karaci\u011fer metastazlar\u0131n\u0131 saptayabilmek i\u00e7in optimize edilmelidir.<\/span><\/p>\n

        \u0130mm\u00fcnohistokimyasal ve Ga-68 PSMA PET\/BT verileri, artm\u0131\u015f PSMA ekspresyonunun neovask\u00fclarizasyona ba\u011fl\u0131 olarak, kolon kanseri, \u00f6zefagus kanseri, tiroid kanseri, akci\u011fer kanseri, b\u00f6brek h\u00fccreli karsinom ve beyin t\u00fcm\u00f6rleri gibi prostat d\u0131\u015f\u0131 kanser t\u00fcrlerinde de rastlanabildi\u011fini g\u00f6stermi\u015ftir.<\/span><\/p>\n

        \u00d6nemli bir di\u011fer tuzak ise retroperitoneal lenf nodu metastaz\u0131 \u015feklinde yanl\u0131\u015f yorumlanmaya neden olabilen otonom sinir sisteminin \u00e7\u00f6lyak gangliyonlar\u0131nda Ga-68 PSMA ligand tutulumudur. <\/span><\/p>\n

        Ga-68 PSMA PET\/BT, prostat kanseri hastalar\u0131nda tedaviye yan\u0131t\u0131n de\u011ferlendirilmesi i\u00e7in hen\u00fcz konfirme edilmemi\u015ftir. Bununla birlikte prensip olarak, tedaviye yan\u0131t\u0131n de\u011ferlendirilmesi i\u00e7in kullan\u0131laca\u011f\u0131 durumlarda, PSMA tutulumunun yayg\u0131nl\u0131\u011f\u0131 ve yo\u011funlu\u011fu raporlanarak \u00f6nceki g\u00f6r\u00fcnt\u00fclemeleri ile kar\u015f\u0131la\u015ft\u0131r\u0131lmal\u0131d\u0131r.<\/span><\/p>\n

        miPSMA ekspresyon skorlamas\u0131 ( <\/b><\/span>Ga-68 PSMA<\/b><\/span> i\u00e7in)<\/b><\/span><\/p>\n\n\n\n\n\n\n\n
        \n

        Skor<\/b><\/span><\/p>\n<\/td>\n

        		\n

        Raporlama<\/b><\/span><\/p>\n<\/td>\n

        		\n

        Tutulum D\u00fczeyi <\/span><\/b><\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        0<\/span><\/p>\n<\/td>\n

        		\n

        yok <\/span> <\/span><\/span><\/p>\n<\/td>\n

        		\n

        < kan havuzu<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        1<\/span><\/p>\n<\/td>\n

        		\n

        hafif <\/span><\/span><\/p>\n<\/td>\n

        		\n

        \u2265 kan havuzu ve < karaci\u011fer*<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        2<\/span><\/p>\n<\/td>\n

        		\n

        orta <\/span><\/span><\/p>\n<\/td>\n

        		\n

        \u2265karaci\u011fer ve < parotis gland\u0131<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        3<\/span><\/p>\n<\/td>\n

        		\n

        y\u00fcksek\u00a0 <\/span><\/span><\/span><\/p>\n<\/td>\n

        		\n

        \u2265 parotis gland\u0131<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

        *18F-PSMA gibi karaci\u011ferden ekskresyona u\u011frayan PSMA ligandlar\u0131 kullan\u0131ld\u0131\u011f\u0131nda, referans organ olarak karaci\u011fer yerine dalak \u00f6nerilmektedir.\u00a0<\/span><\/p>\n

        Ga-68 PSMA PET\/BT i\u00e7in miTNM s\u0131n\u0131fland\u0131rmas\u0131<\/b> <\/span><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
        \n

        S\u0131n\u0131f\u00a0 <\/span><\/span><\/b><\/span><\/p>\n<\/td>\n

        		\n

        A\u00e7\u0131klama<\/b><\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        Lokal t\u00fcm\u00f6r (T)<\/span><\/p>\n<\/td>\n

        		\n

        \n<\/td>\n<\/tr>\n

        \n

        miT0 <\/span> <\/span> <\/span> <\/span><\/span><\/p>\n<\/td>\n

        		\n

        Lokal t\u00fcm\u00f6r yok<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        miT2 <\/span> <\/span> <\/span> <\/span><\/span><\/p>\n<\/td>\n

        		\n

        Organa s\u0131n\u0131rl\u0131 t\u00fcm\u00f6r, intraprostatik t\u00fcm\u00f6r yerle\u015fimi sekstant baz\u0131nda raporlan\u0131r.<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        u<\/span><\/p>\n<\/td>\n

        		\n

        Tek odakl\u0131<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        m <\/span><\/span><\/p>\n<\/td>\n

        		\n

        \u00c7ok odakl\u0131<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        miT3 <\/span> <\/span> <\/span> <\/span><\/span><\/p>\n<\/td>\n

        		\n

        Organa s\u0131n\u0131rl\u0131 olmayan t\u00fcm\u00f6r, intraprostatik t\u00fcm\u00f6r yerle\u015fimi sekstant baz\u0131nda raporlan\u0131r.<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        a <\/span> <\/span> <\/span> <\/span><\/span><\/p>\n<\/td>\n

        		\n

        Kaps\u00fcl d\u0131\u015f\u0131na uzan\u0131m <\/span><\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        b <\/span> <\/span> <\/span> <\/span><\/span><\/p>\n<\/td>\n

        		\n

        T\u00fcm\u00f6r seminal vezik\u00fcllere invaze<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        miT4 <\/span><\/span><\/p>\n<\/td>\n

        		\n

        T\u00fcm\u00f6r seminal vezik\u00fcller d\u0131\u015f\u0131nda eksternal sfinkter, rektum, mesane, levator kas\u0131 veya pelvik duvar gibi kom\u015fu yap\u0131lara invaze <\/span><\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        miTr<\/span><\/p>\n<\/td>\n

        		\n

        Radikal prostatektomi sonras\u0131 lokal n\u00fcks varl\u0131\u011f\u0131<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        B\u00f6lgesel lenf nodlar\u0131 (N)<\/span><\/p>\n<\/td>\n

        		\n

        \n<\/td>\n<\/tr>\n

        \n

        miN0<\/span><\/p>\n<\/td>\n

        		\n

        Pozitif lenf nodu yok<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        miN1a <\/span><\/span><\/p>\n<\/td>\n

        		\n

        Lenf nodu metastaz\u0131 tek lenf nodu b\u00f6lgesinde, standard istasyon baz\u0131nda raporlan\u0131r.<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        miN1b <\/span><\/span><\/p>\n<\/td>\n

        		\n

        Lenf nodu metastaz\u0131 \u2265 2 lenf nodu b\u00f6lgesinde, standard istasyon baz\u0131nda raporlan\u0131r.<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        Uzak metastaz (M)<\/span><\/p>\n<\/td>\n

        		\n

        \n<\/td>\n<\/tr>\n

        \n

        miM0 <\/span> <\/span> <\/span> <\/span><\/span><\/p>\n<\/td>\n

        		\n

        Uzak metastaz yok<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        miM1 <\/span> <\/span> <\/span> <\/span><\/span><\/p>\n<\/td>\n

        		\n

        Uzak metastaz<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        a<\/span><\/p>\n<\/td>\n

        		\n

        Ekstrapelvik lenf nodu metastaz\u0131, standard istasyon baz\u0131nda raporlan\u0131r.<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        b<\/span><\/p>\n<\/td>\n

        		\n

        Kemik metastaz\u0131, tutulum paterni ve tek odakl\u0131 yada oligometastatik durumda tutulan kemikler raporlan\u0131r.<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        c<\/span><\/p>\n<\/td>\n

        		\n

        Di\u011fer b\u00f6lgelerde; ayr\u0131ca tutulmu\u015f organ raporlan\u0131r.<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n


        Ga-68 PSMA PET\/BT i\u00e7in prostat bezinin sekstant segmentasyonu<\/b><\/span><\/p>\n\n\n\n\n\n\n\n\n\n
        \n

        Segment <\/span> <\/span> <\/span><\/b><\/span><\/p>\n<\/td>\n

        		\n

        miT2-4 i\u00e7in \u015fablon<\/b><\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        LB <\/span> <\/span> <\/span> <\/span><\/span><\/p>\n<\/td>\n

        		\n

        Sol bazal<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        RB <\/span> <\/span> <\/span> <\/span><\/span><\/p>\n<\/td>\n

        		\n

        Sa\u011f bazal<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        LM <\/span> <\/span> <\/span> <\/span><\/span><\/p>\n<\/td>\n

        		\n

        Sol orta<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        RM <\/span> <\/span> <\/span> <\/span><\/span><\/p>\n<\/td>\n

        		\n

        Sa\u011f orta<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        LA <\/span> <\/span> <\/span> <\/span><\/span><\/p>\n<\/td>\n

        		\n

        Sol apeks<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        RA <\/span> <\/span> <\/span> <\/span><\/span><\/p>\n<\/td>\n

        		\n

        Sa\u011f apeks<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

        Lenf nodu istasyonlar\u0131<\/b><\/span><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
        \n

        istasyon <\/span><\/span><\/p>\n<\/td>\n

        		\n

        \n<\/td>\n<\/tr>\n

        \n

        miN1a\/b <\/span><\/span><\/p>\n<\/td>\n

        		\n

        \n<\/td>\n<\/tr>\n

        \n

        \n<\/td>\n

        		\n

        \u0130nternal iliak <\/span><\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        \n<\/td>\n

        		\n

        Eksternal iliak <\/span><\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        \n<\/td>\n

        		\n

        Ana iliak <\/span><\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        \n<\/td>\n

        		\n

        Obturator<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        \n<\/td>\n

        		\n

        Presakral<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        \n<\/td>\n

        		\n

        Di\u011fer, pelvik (tan\u0131mla)<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        miM1a<\/span><\/p>\n<\/td>\n

        		\n

        \n<\/td>\n<\/tr>\n

        \n

        \n<\/td>\n

        		\n

        Retroperitoneal <\/span> <\/span><\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        \n<\/td>\n

        		\n

        Supradiyafragmatik <\/span><\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        \n<\/td>\n

        		\n

        Di\u011fer, ekstrapelvik<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n


        Kemik tutulum paterleri<\/b><\/span><\/p>\n\n\n\n\n\n\n
        \n

        Tek odakl\u0131<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        Oligometastatik (n \u2264 3) <\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        Dissemine<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        Diff\u00fcz kemik ili\u011fi tutulumu<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

        [\/et_pb_accordion_item][et_pb_accordion_item title=“TEDAV\u0130 H\u0130ZMETLER\u0130 – LUTESYUM-177 PSMA TEDAV\u0130S\u0130“ open_toggle_text_color=“#0ca7c5″ _builder_version=“4.4.8″ toggle_font=“|700|||||||“ toggle_font_size=“18px“ open=“off“]<\/p>\n

        Endikasyon<\/b><\/span><\/p>\n

         <\/p>\n

        Lu-177 PSMA tedavisi; metastatik kastrasyona diren\u00e7li prostat kanserli hastalarda, onaylanm\u0131\u015f standart tedavi y\u00f6ntemlerinin t\u00fckendi\u011fi veya uygun olmad\u0131\u011f\u0131 durumlarda endikedir.<\/span><\/p>\n

         <\/p>\n

        Lutesyum-177 PSMA Tedavisi Nedir?<\/b><\/span><\/p>\n

         <\/p>\n

        Teranostik t\u0131p d\u00fcnyas\u0131nda yeni geli\u015fmekte olan bir aland\u0131r. T\u00fcm\u00f6re \u00f6zg\u00fcl bir ila\u00e7 ile g\u00f6r\u00fcnt\u00fcleme yaparak saptanan t\u00fcm\u00f6r ve metastazlar\u0131n\u0131n, nereye gidece\u011fi-ne kadar gidece\u011fi ve hastal\u0131kl\u0131 dokuyu etkileme g\u00fcc\u00fc \u00f6nceden bilinen yine \u00f6zg\u00fcl bir ila\u00e7 ile tedavi edilebildi\u011fi bir yakla\u015f\u0131md\u0131r. Bu yakla\u015f\u0131m, geleneksel t\u0131ptan ki\u015fiye \u00f6zg\u00fc \u00e7a\u011fda\u015f t\u0131p uygulamalar\u0131na ge\u00e7i\u015f yap\u0131lmas\u0131n\u0131 sa\u011flamaktad\u0131r. Prostat kanserinde, bir yandan Ga-68 PSMA PET\/BT ile prostat kanserine ait t\u00fcm\u00f6ral dokular y\u00fcksek duyarl\u0131l\u0131k ve \u00f6zg\u00fcll\u00fckte g\u00f6r\u00fcnt\u00fclenebilmekte, di\u011fer yandan Lu-177 PSMA ile bu t\u00fcm\u00f6ral dokular\u0131n \u00f6zg\u00fcl ve hedefe y\u00f6nelik tedavisi yap\u0131labilmektedir. Bu, teranostik uygulamalar i\u00e7in olduk\u00e7a ba\u015far\u0131l\u0131 ve yeni bir y\u00f6ntemdir. <\/span><\/p>\n

         <\/p>\n

        \u0130lk PSMA hedefli Lu-177 PSMA-RLT, Nisan 2013’te Bad Berka-Almanya’da ba\u015far\u0131yla ger\u00e7ekle\u015ftirilmi\u015ftir. Bu ilk teranostik PSMA hedefli bile\u015fik; PSMA I&T (g\u00f6r\u00fcnt\u00fcleme ve tedavi \u201cimaging and therapy\u201d) olarak adland\u0131r\u0131lm\u0131\u015f ve bu ligand daha sonra \u00e7e\u015fitli merkezlerde hem Ga-68 ile g\u00f6r\u00fcnt\u00fcleme hem de 177Lu ile radyoligand tedavi i\u00e7in kullan\u0131lm\u0131\u015ft\u0131r.\u00a0<\/span><\/p>\n

         <\/p>\n

        Lutesyum-177 PSMA Nas\u0131l Tedavi Eder?<\/b><\/span><\/p>\n

         <\/p>\n

        PSMA, di\u011fer ad\u0131yla glutamat karboksipeptidaz II (GCPII), \u00e7ok say\u0131da h\u00fccresel fonksiyona sahip, sa\u011fl\u0131kl\u0131 prostat h\u00fccre zar\u0131nda bulunan bir protein t\u00fcr\u00fcd\u00fcr. Her ne kadar sa\u011fl\u0131kl\u0131 prostat h\u00fccreleri do\u011fal olarak \u00e7ok d\u00fc\u015f\u00fck seviyelerde PSMA olu\u015ftursa da, kanserli prostat t\u00fcm\u00f6rleri son derece y\u00fcksek seviyelerde (genellikle normal prostat h\u00fccresinden 1000 kat daha y\u00fcksek) PSMA olu\u015fturmaktad\u0131r. Prostat kanserinin v\u00fccudun di\u011fer b\u00f6lgelerindeki metastazlar\u0131 i\u00e7in de bu durum ge\u00e7erlidir. 177L atomu, PSMA ad\u0131 verilen ta\u015f\u0131y\u0131c\u0131 molek\u00fcle eklenebilen, radyoaktif beta par\u00e7ac\u0131klar\u0131 g\u00f6nderen radyoaktif bir elementtir. Lu-177 PSMA damar yoluyla uyguland\u0131\u011f\u0131nda, PSMA’n\u0131n bulundu\u011fu t\u00fcm t\u00fcm\u00f6r dokular\u0131na gider ve bu kanser h\u00fccrelerini radyasyon yayarak yok eder. Lu-177 PSMA tedavisi kanser dokusunu hedef ald\u0131\u011f\u0131ndan, v\u00fccudun di\u011fer b\u00f6lgelerinde al\u0131nan \u0131\u015f\u0131n dozu \u00e7ok az d\u00fczeylerde olur. Lu-177 PSMA’n\u0131n t\u00fcm\u00f6r h\u00fccreleri taraf\u0131ndan tutulmayan k\u0131sm\u0131 ise t\u00fck\u00fcr\u00fck, idrar ve d\u0131\u015fk\u0131ya ge\u00e7erek v\u00fccuttan at\u0131l\u0131r. <\/span><\/p>\n

         <\/p>\n

        Lu-177 PSMA tedavisi; konusunda uzman, multidisipliner bir ekibin de\u011ferlendirmeleri sonras\u0131nda uygulanmaktad\u0131r. <\/span><\/p>\n

         <\/p>\n

        Lu-177 PSMA tedavisi, ABD ve Avrupa’daki ticari olmayan, akademik, ara\u015ft\u0131rma ortamlar\u0131nda geli\u015ftirilmi\u015ftir. Yak\u0131n zamanda ise hekimlerin tedavi etme cesareti, \u00e7abalar\u0131 ve elbette ki onlar\u0131n tedavi edilemez, \u00f6l\u00fcmc\u00fcl hastal\u0131ktan muzdarip hastalar\u0131 ile klinik prati\u011fe ge\u00e7mi\u015ftir. Bu durum, baz\u0131 Avrupa \u00fclkelerinde 1990’lar\u0131n ortas\u0131nda sunulan n\u00f6roendokrin t\u00fcm\u00f6rlerin peptit resept\u00f6r\u00fc radyon\u00fcklid tedavisi (PRRT) ile benzer bir s\u00fcre\u00e7tir. Ancak, PRRT gibi ba\u015far\u0131s\u0131 kan\u0131tlanm\u0131\u015f bir tedavinin bile EMA ve FDA onaylar\u0131n\u0131 almas\u0131 15 y\u0131ldan fazla zaman alm\u0131\u015ft\u0131r. Dozimetri ve ba\u015flang\u0131\u00e7 sonu\u00e7lar\u0131 benzer \u015fekilde Lu-177 PSMA tedavisi i\u00e7in de umut vericidir.<\/span><\/p>\n

         <\/p>\n

        Metastatik CRPC (mCRPC) hastalar\u0131nda Lu-177 PSMA tedavisinin etkinli\u011fini de\u011ferlendiren devam eden bir faz 3 \u00e7al\u0131\u015fma (VISION) olmas\u0131na ra\u011fmen, PSMA tedavisi \u015fu an i\u00e7in sadece mCRPC i\u00e7in k\u0131lavuzlar taraf\u0131ndan \u00f6nerilen, onaylanm\u0131\u015f tedavilerin ard\u0131ndan uygulanacak deneysel bir tedavi yakla\u015f\u0131m\u0131d\u0131r. <\/span><\/p>\n

         <\/p>\n

        Prostat kanserinde onaylanm\u0131\u015f tedaviler; abirateron ve enzalutamid kullanan yeni nesil hormon tedavileri (medyan sa\u011f kal\u0131m\u0131, s\u0131ras\u0131yla 3.9 ay ve 4.8 aya kadar uzatan) ile s\u0131kl\u0131kla yan etkiye yola a\u00e7an ancak genel sa\u011f kal\u0131m\u0131 sadece birka\u00e7 ay uzatabilen dosetaksel ve cabazitaksel kullanan birinci ve ikinci basamak kemoterapilerdir. <\/span><\/p>\n

         <\/p>\n

        Ayr\u0131ca, sadece yayg\u0131n veya a\u011fr\u0131l\u0131 osteoblastik kemik metastazlar\u0131 hedefleyen ve nodal ya da viseral metastazlar\u0131 tedavi etmeyen 223Radyum-klor\u00fcr ise medyan genel sa\u011f kal\u0131m\u0131 3,6 ay artt\u0131r\u0131r. 223Radyum tedavisi, herhangi bir visseral veya lenf nodu metastaz\u0131 olmayan, birden fazla a\u011fr\u0131l\u0131 kemik metastaz\u0131 bulunan hastalarda, \u00fc\u00e7\u00fcnc\u00fc basamak tedavi olarak kullan\u0131lmal\u0131d\u0131r. <\/span><\/p>\n

         <\/p>\n

        Kemoterapinin kontrendike oldu\u011fu baz\u0131 hastalarda, Lu-177 PSMA tedavisi abirateron\/enzalutamid’den sonra kullan\u0131labilir.<\/span><\/p>\n

         <\/p>\n

        Tedavi Etkinli\u011fi<\/b><\/span><\/p>\n

         <\/p>\n

        Bir t\u00fcm\u00f6r marker olarak PSA, farkl\u0131 prostat kanseri tedavilerinde, tedaviye yan\u0131t\u0131n de\u011ferlendirilmesinde en s\u0131k kullan\u0131lan parametrelerden biridir. Lu-177 PSMA tedavisi sonras\u0131 etkinlik, \u00e7e\u015fitli metaanalizler ve g\u00f6zlemsel \u00e7al\u0131\u015fmalarla de\u011ferlendirilmi\u015ftir. Lu-177 PSMA tedavisi sonras\u0131, PSA’da %50 ve daha fazla azalma olarak tan\u0131mlanan, biyokimyasal yan\u0131t, hastalar\u0131n yar\u0131s\u0131ndan fazlas\u0131nda izlenir. Hastalar\u0131n \u00fc\u00e7te birinden fazlas\u0131nda da g\u00f6r\u00fcnt\u00fclemede k\u0131smi yan\u0131t mevcuttur. Yak\u0131n zamanda yap\u0131lan bir faz II \u00e7al\u0131\u015fmas\u0131nda, hastalar\u0131n %57’sinde, PSA’da %50 veya daha fazla d\u00fc\u015f\u00fc\u015f g\u00f6sterilmi\u015ftir. \u00d6l\u00e7\u00fclebilir hastal\u0131\u011f\u0131 olan hastalar\u0131n %82’sinde de g\u00f6r\u00fcnt\u00fcleme yoluyla, nodal veya viseral hastal\u0131kta objektif yan\u0131t bildirilmi\u015ftir. Mevcut veriler, Lu-177 PSMA-617 ve Lu-177 PSMA I&T ligandlar\u0131 aras\u0131nda, etkinlik a\u00e7\u0131s\u0131ndan farkl\u0131l\u0131k olmad\u0131\u011f\u0131n\u0131 g\u00f6stermektedir. Viseral metastaz ve serum alkalen fosfataz \u2265 220 U\/L varl\u0131\u011f\u0131 ise k\u00f6t\u00fc prognoz ile ili\u015fkili bulunmu\u015ftur. K\u00fc\u00e7\u00fck g\u00f6zlemsel \u00e7al\u0131\u015fmalarda, hastalar\u0131n yar\u0131s\u0131ndan fazlas\u0131nda, a\u011fr\u0131 ve ya\u015fam kalitesinin \u00f6nemli \u00f6l\u00e7\u00fcde iyile\u015fti\u011fi g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. <\/span><\/p>\n

         <\/p>\n

        2016’da insanda ilk kez kullan\u0131lan Ac-225 PSMA ile ilgili halen az say\u0131da yay\u0131nlanm\u0131\u015f \u00e7al\u0131\u015fma bulunmaktad\u0131r. Ac-225 PSMA’da daha y\u00fcksek yan\u0131t oran\u0131 ile birlikte daha y\u00fcksek oranda a\u011f\u0131z kurulu\u011fu da bildirilmektedir. Bu yan etki ile ba\u015fa \u00e7\u0131kabilmek i\u00e7in Ac-225 PSMA ve Lu-177 PSMA’n\u0131n birlikte kullan\u0131ld\u0131\u011f\u0131 tandem tedavi protokolleri \u00fczerinde \u00e7al\u0131\u015f\u0131lmaktad\u0131r. <\/span><\/p>\n

         <\/p>\n

        PSMA \u0130\u015faretlemede Kullan\u0131lan Radyoaktif Elementler <\/b><\/span><\/p>\n

         <\/p>\n

        Lutesyum-177 (Lu-177), gama ve beta \u0131\u015f\u0131mas\u0131 yapan, 6.7 g\u00fcnl\u00fck yar\u0131lanma \u00f6mr\u00fcne sahip radyoaktif bir elementtir. Yayd\u0131\u011f\u0131 d\u00fc\u015f\u00fck beta par\u00e7ac\u0131klar\u0131n\u0131n (maksimum enerjisi 0.5 MeV) kat etti\u011fi ortalama mesafe 0,7 mm, yumu\u015fak dokuda kat etti\u011fi maksimum mesafe ise 2,1 mm’dir. Tedavi sonras\u0131 g\u00f6r\u00fcnt\u00fclemede kullan\u0131lan, gama emisyonlar\u0131n\u0131n oldu\u011fu enerji pikleri 112.9 keV ve 208.4 keV’dir. 177Lutesyum d\u00fcnya \u00e7ap\u0131nda PSMA tedavisi i\u00e7in en s\u0131k kullan\u0131lan radyoaktif elementtir ve yay\u0131nlanan PSMA tedavisi verilerinin \u00e7o\u011funlu\u011fu; Lu-177 PSMA-617 ve Lu-167 I & T ligandlar\u0131n\u0131 kullanan tedavilere dayanmaktad\u0131r.<\/span><\/p>\n

         <\/p>\n

        Aktinyum-225 (Ac-225), 10 g\u00fcnl\u00fck yar\u0131lanma \u00f6mr\u00fc ve yayd\u0131\u011f\u0131 6 MeV enerjiye sahip alfa par\u00e7ac\u0131\u011f\u0131yla, PSMA tedavisi i\u00e7in en s\u0131k kullan\u0131lan ikinci radyoaktif elementtir. Ac-225 PSMA hedefli alfa tedavisi, bir alfa par\u00e7ac\u0131\u011f\u0131n\u0131n, beta par\u00e7ac\u0131\u011f\u0131na g\u00f6re \u00e7ok daha k\u0131sa doku penetrasyon aral\u0131\u011f\u0131na sahip olmas\u0131 nedeniyle, k\u0131rm\u0131z\u0131 kemik ili\u011fi infiltrasyonu varl\u0131\u011f\u0131nda daha uygun bir mikrodozimetriyi m\u00fcmk\u00fcn k\u0131lar. Bu da, g\u00f6r\u00fcnt\u00fclemelerinde \u201csuperscan\u201d paterni ile ba\u015fvuran hastalar i\u00e7in iyi bir tercih olabilir. Ayr\u0131ca, Lu-177 PSMA tedavisini kar\u015f\u0131 diren\u00e7 geli\u015fimi durumunda, Ac-225 PSMA-hedefli alfa tedavisi, ilave bir eskalasyon ad\u0131m\u0131 olarak da uygulanm\u0131\u015ft\u0131r. <\/span><\/p>\n

         <\/p>\n

        Radyofarmas\u00f6tikler<\/b><\/span><\/p>\n

         <\/p>\n

        Lu-177 PSMA ligandlar\u0131 t\u0131bbi \u00fcr\u00fcnleri temsil eder ve belirli durumlarda, ulusal d\u00fczenlemeler dikkate al\u0131narak, resmi onay al\u0131nmadan kullan\u0131labilir. Haz\u0131rlan\u0131\u015f ve kalite kontrol (QC) a\u00e7\u0131s\u0131ndan, n\u00f6roendokrin t\u00fcm\u00f6rlerde PRRT kullan\u0131m\u0131 ile ilgili ortak IAEA, EANM ve SNMMI pratik k\u0131lavuzunun \u00f6nerileri dikkate al\u0131nmal\u0131d\u0131r. Bu rehber do\u011frultusunda, serbest Lu-177 kaynakl\u0131 radyokimyasal safs\u0131zl\u0131k %2’den az olmal\u0131 ve kalite kontrol hem y\u00fcksek performansl\u0131 s\u0131v\u0131 kromatografisi hem de anl\u0131k ince tabaka kromatografi y\u00f6ntemlerini i\u00e7ermelidir.<\/span><\/p>\n

         <\/p>\n

        Mevcut klinik bilgi a\u011f\u0131rl\u0131kl\u0131 olarak Lu-177, PSMA-617 ve Lu-177 PSMA I&T olarak adland\u0131r\u0131lan iki d\u00fc\u015f\u00fck molek\u00fcl a\u011f\u0131rl\u0131kl\u0131 PSMA-ligand\u0131na dayanmaktad\u0131r. Beta par\u00e7ac\u0131\u011f\u0131 yayan 177Lu ile radyoaktif olarak i\u015faretlenen bu iki radyoligand, kar\u015f\u0131la\u015ft\u0131r\u0131labilir biyodistrib\u00fcsyon ve dolay\u0131s\u0131yla dozimetrik \u00f6zelliklere sahiptir. Bu nedenle, her iki ligand de\u011fi\u015ftirilebilir olarak uygulanabilir. \u0130kinci nesil ligandlar\u0131n geli\u015ftirilmesine halen devam etmektedir.<\/span><\/p>\n

         <\/p>\n

        Yeni Konseptler<\/b><\/span><\/p>\n

         <\/p>\n

        Metastatik prostat kanserinin hedefe y\u00f6nelik radyoligand tedavisini daha da iyile\u015ftirmek i\u00e7in baz\u0131 yeni kavramlar ara\u015ft\u0131r\u0131lmaktad\u0131r. <\/span><\/p>\n

         <\/p>\n

        T\u00fck\u00fcr\u00fck bezleri ve b\u00f6breklerde PSMA tutulumunu azaltmaya y\u00f6nelik uygulamalar<\/i><\/b><\/span><\/p>\n

         <\/p>\n

        T\u00fck\u00fcr\u00fck bezleri ve b\u00f6breklerde \u0131\u015f\u0131n dozunu azaltmaya y\u00f6nelik a\u015fa\u011f\u0131daki \u00e7\u00f6z\u00fcm aray\u0131\u015flar\u0131 uygulanm\u0131\u015fsa da s\u0131n\u0131rl\u0131 ba\u015far\u0131 elde edilebilmi\u015ftir:<\/span><\/p>\n

         <\/p>\n

        T\u00fck\u00fcr\u00fck bezleri i\u00e7in;<\/span><\/p>\n

         <\/p>\n

        -Giri\u015fimsel sialendoskopi ile kanal geni\u015fletilmesi, salin irrigasyonu, steroid enjeksiyonu<\/span><\/p>\n

         <\/p>\n

        -Botulinum toksininin intraparankimal enjeksiyonu<\/span><\/p>\n

         <\/p>\n

        -Buz torbalar\u0131 ile t\u00fck\u00fcr\u00fck bezlerini d\u0131\u015far\u0131dan so\u011futma <\/span><\/p>\n

         <\/p>\n

        B\u00f6brekler i\u00e7in; <\/span><\/p>\n

         <\/p>\n

        2-PMPA (selektif glutamat karboksipeptidaz II inhibit\u00f6r\u00fc) ve mannitol kullan\u0131mlar\u0131 ara\u015ft\u0131r\u0131lm\u0131\u015fsa da bu y\u00f6ntemlerin hi\u00e7biri geni\u015f hasta serisine uygulanmam\u0131\u015ft\u0131r. Her ek m\u00fcdahale, komplikasyon riskini art\u0131rd\u0131\u011f\u0131ndan veya kendi yan etkilerini ortaya \u00e7\u0131karabilece\u011finden, bu deneysel yakla\u015f\u0131mlar\u0131n hi\u00e7biri, bug\u00fcn rutin uygulama i\u00e7in \u00f6nerilememektedir.<\/span><\/p>\n

         <\/p>\n

        Plazma proteinlerine ba\u011flanma ile t\u00fcm\u00f6r PSMA tutulumunu art\u0131rma \u00e7al\u0131\u015fmalar\u0131<\/i><\/b><\/span><\/p>\n

         <\/p>\n

        Farmas\u00f6tiklerin plazma proteinlerine ba\u011flanmas\u0131n\u0131n art\u0131r\u0131lmas\u0131, spesifik ila\u00e7 tutulumunu geli\u015ftirirken klirens oran\u0131n\u0131 azaltan etkili bir strateji olabilmektedir. Bu bilgi \u0131\u015f\u0131\u011f\u0131nda, artm\u0131\u015f alb\u00fcmine ba\u011flanma ve yava\u015flam\u0131\u015f klirens kineti\u011fi ile PSMA radyoligandlar\u0131n\u0131n kullan\u0131m\u0131, tedavi ama\u00e7l\u0131 t\u00fcm\u00f6ral tutulumu iyile\u015ftirmek i\u00e7in umut verici bir yakla\u015f\u0131m olarak \u00f6nerilmi\u015ftir. Ancak t\u00fcm\u00f6ral PSMA tutulumundaki bu pozitif etkiyle paralel, sa\u011fl\u0131kl\u0131 organlarda istenmeyen artm\u0131\u015f PSMA tutulumunun g\u00f6r\u00fclmesi, \u00e7\u00f6z\u00fclmesi gereken bir sorundur. <\/span><\/p>\n

         <\/p>\n

        Radyohibrit PSMA ligandlar (rhPSMA)<\/i><\/b><\/span><\/p>\n

         <\/p>\n

        18<\/sup><\/span>F veya radyometaller ile i\u015faretli PSMA gibi peptit ve peptit benzeri radyofarmas\u00f6tiklerin h\u0131zl\u0131 ve verimli bir \u015fekilde i\u015faretlenmesine olanak tan\u0131yan bir platform teknolojisi sa\u011flamak amac\u0131yla, yak\u0131n zamanda radyohibrit PSMA ligandlar\u0131 (rhPSMA) olarak adland\u0131r\u0131lan benzersiz ve yeni bir radyofarmas\u00f6tik s\u0131n\u0131f\u0131 geli\u015ftirilmi\u015ftir. rhPSMA ligandlar\u0131n\u0131n benzersiz bir \u00f6zelli\u011fi, bu ligandlar\u0131n kovalent olarak ba\u011fl\u0131 hem flor hem de metal kompleksi i\u00e7ermeleridir. Bu ama\u00e7la de\u011fi\u015fimli olarak radyoaktif ve non-radyoaktif izotoplar kullan\u0131lmaktad\u0131r (\u00d6rn.; [<\/span>19<\/sup><\/span>F][<\/span>177<\/sup><\/span>Lu]rhPSMA ve [<\/span>18<\/sup><\/span>F][<\/span>nat<\/sup><\/span>Lu]rhPSMA). Kimyasal olarak \u00f6zde\u015f iki liganddan\u00a0 <\/span>[<\/span>18<\/sup><\/span>F][<\/span>nat<\/sup><\/span>Lu]rhPSMA tedavi \u00f6ncesi g\u00f6r\u00fcnt\u00fcleme, dozimetri ve tedaviye yan\u0131t\u0131n de\u011ferlendirilmesinde kullan\u0131l\u0131rken,\u00a0 <\/span>ikizi olan [<\/span>19<\/sup><\/span>F][<\/span>177<\/sup><\/span>Lu]rhPSMA tedavide kullan\u0131lmaktad\u0131r. <\/span><\/p>\n

         <\/p>\n

        Lutesyum-177 PSMA Tedavisi G\u00fcvenli midir?<\/b><\/span><\/p>\n

         <\/p>\n

        Lu-177 PSMA tedavisi i\u00e7in uygun bir g\u00fcvenlik profili mevcuttur.<\/span><\/p>\n

         <\/p>\n

        Lu-177 PSMA tedavisi g\u00fcvenli\u011fi, \u00e7e\u015fitli g\u00f6zlemsel \u00e7al\u0131\u015fmalar\u0131n bir par\u00e7as\u0131 olarak bildirilmi\u015ftir. Bu \u00e7al\u0131\u015fmalarda, grade 3-4 hematotoksisitenin hastalar\u0131n %10’undan daha az\u0131nda meydana geldi\u011fi g\u00f6r\u00fclmektedir. Ba\u015flang\u0131\u00e7taki d\u00fc\u015f\u00fck kan say\u0131m\u0131 seviyeleri ve yayg\u0131n kemik ili\u011fi tutulumu, bireysel olarak hastalarda ciddi hematotoksisite ile ili\u015fkilendirilmi\u015ftir. Bununla birlikte, grade 3-4 yan etkilerin oran\u0131, t\u00fcm di\u011fer kategoriler i\u00e7in, t\u00fck\u00fcr\u00fck bezi fonksiyonu da dahil olmak \u00fczere, %5’ten azd\u0131r. Hastalar\u0131n %87’sinde 1. derece a\u011f\u0131z kurulu\u011fu, %50’sinde 1. veya 2. derece ge\u00e7ici bulant\u0131 ve %50’sinde de 1. veya 2. derece yorgunluk g\u00f6r\u00fclebilmektedir. Lu-177 PSMA-617 ile ili\u015fkili olabilecek en yayg\u0131n toksik etkiler, %37 oran\u0131nda 3. derece lenfositopeni, %13 oran\u0131nda 3. derece anemi ve %13 oran\u0131nda 3 veya 4. derece trombositopeni olarak bildirilmi\u015ftir. \u00d6zetle, veriler Lu-177 PSMA tedavisi i\u00e7in uygun bir g\u00fcvenlik profilini g\u00f6stermektedir.<\/span><\/p>\n

         <\/p>\n

        Nefrotoksisite<\/b><\/span><\/p>\n

         <\/p>\n\n\n\n\n
        \n

        Derece<\/b><\/span><\/p>\n<\/td>\n

        		\n

        0<\/span><\/p>\n<\/td>\n

        		\n

        1<\/span><\/p>\n<\/td>\n

        		\n

        2<\/span><\/p>\n<\/td>\n

        		\n

        3<\/span><\/p>\n<\/td>\n

        		\n

        4<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        Kreatinin<\/b><\/span><\/p>\n<\/td>\n

        		\n

        NS<\/span><\/p>\n<\/td>\n

        		\n

        \u22641.5xN <\/span><\/span><\/p>\n<\/td>\n

        		\n

        1.5-3.0xN<\/span><\/p>\n<\/td>\n

        		\n

        3.1-6.0xN<\/span><\/p>\n<\/td>\n

        		\n

        >6.0xN<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

         <\/p>\n


        NS: normal s\u0131n\u0131rlarda, N normal<\/span><\/p>\n

         <\/p>\n

        Kserostomi (A\u011f\u0131z kurulu\u011fu)<\/b><\/span><\/p>\n

         <\/p>\n\n\n\n\n\n
        \n

        1. Derece<\/b><\/span><\/p>\n<\/td>\n

        		\n

        Semptomatik, ancak ciddi diyet de\u011fi\u015fikli\u011fine ihtiya\u00e7 yok (\u00f6rn. kuru veya kal\u0131n t\u00fck\u00fcr\u00fck); uyar\u0131lmam\u0131\u015f t\u00fck\u00fcr\u00fck ak\u0131\u015f\u0131> 0.2 mL \/ dk.\u2019d\u0131r<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        2. Derece<\/b><\/span><\/p>\n<\/td>\n

        		\n

        Orta \u015fiddette semptomlar; oral al\u0131m de\u011fi\u015fiklikleri var (\u00f6rn. bol su, di\u011fer kayganla\u015ft\u0131r\u0131c\u0131lara ihtiya\u00e7 duyulur. P\u00fcreler ve\/veya yumu\u015fak, sulu g\u0131dalarla s\u0131n\u0131rl\u0131 diyet); uyar\u0131lmam\u0131\u015f t\u00fck\u00fcr\u00fck 0.1 ila 0.2 mL \/ dk.’d\u0131r.<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        3. Derece<\/b><\/span><\/p>\n<\/td>\n

        		\n

        Oral yolla yeterince beslenme yoktur. T\u00fcple ya da parenteral yolla beslenme gereklidir; uyar\u0131lmam\u0131\u015f t\u00fck\u00fcr\u00fck <0.1 mL \/ dk.’d\u0131r.<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

         <\/p>\n

        <\/b><\/span><\/p>\n

         <\/p>\n

        Hematotoksisite \/ Kemik ili\u011fi toksisitesi<\/b> <\/span><\/p>\n

         <\/p>\n\n\n\n\n\n\n\n\n\n\n
        \n

        Derece <\/span><\/p>\n<\/td>\n

        		\n

        0<\/span><\/p>\n<\/td>\n

        		\n

        1<\/span><\/p>\n<\/td>\n

        		\n

        2<\/span><\/p>\n<\/td>\n

        		\n

        3<\/span><\/p>\n<\/td>\n

        		\n

        4<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        L\u00f6kosit<\/b><\/span><\/p>\n<\/td>\n

        		\n

        \u22654<\/span><\/p>\n<\/td>\n

        		\n

        3.0-3.9<\/span><\/p>\n<\/td>\n

        		\n

        2.0-2.9 <\/span><\/span><\/p>\n<\/td>\n

        		\n

        1.0-1.9<\/span><\/p>\n<\/td>\n

        		\n

        <1.0<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        Trombosit<\/b><\/span><\/p>\n<\/td>\n

        		\n

        NS<\/span><\/p>\n<\/td>\n

        		\n

        75.0-N<\/span><\/p>\n<\/td>\n

        		\n

        50.0-74.9<\/span><\/p>\n<\/td>\n

        		\n

        25.0-49.9<\/span><\/p>\n<\/td>\n

        		\n

        <25.0<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        Hemoglobin<\/b><\/span><\/p>\n<\/td>\n

        		\n

        NS<\/span><\/p>\n<\/td>\n

        		\n

        10.0-N<\/span><\/p>\n<\/td>\n

        		\n

        8.0-10.0<\/span><\/p>\n<\/td>\n

        		\n

        6.5-7.9<\/span><\/p>\n<\/td>\n

        		\n

        <6.5<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        Gran\u00fclosit<\/b><\/span><\/p>\n<\/td>\n

        		\n

        \u22652.0<\/span><\/p>\n<\/td>\n

        		\n

        1.5-1.9<\/span><\/p>\n<\/td>\n

        		\n

        1.0-1.2 <\/span><\/span><\/p>\n<\/td>\n

        		\n

        0.5-0.9<\/span><\/p>\n<\/td>\n

        		\n

        <0.5<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        Lenfosit<\/b><\/span><\/p>\n<\/td>\n

        		\n

        \u22652.0<\/span><\/p>\n<\/td>\n

        		\n

        1.5-1.9<\/span><\/p>\n<\/td>\n

        		\n

        1.0-1.2 <\/span><\/span><\/p>\n<\/td>\n

        		\n

        0.5-0.9<\/span><\/p>\n<\/td>\n

        		\n

        <0.5<\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        Enfeksiyon<\/b><\/span><\/p>\n<\/td>\n

        		\n

        yok<\/b><\/span><\/p>\n<\/td>\n

        		\n

        hafif<\/b><\/span><\/p>\n<\/td>\n

        		\n

        orta<\/b><\/span><\/p>\n<\/td>\n

        		\n

        ciddi<\/b><\/span><\/p>\n<\/td>\n

        		\n

        ya\u015flam tehdidi<\/b><\/span><\/p>\n<\/td>\n<\/tr>\n

        \n

        Hemoraji<\/b><\/span><\/p>\n<\/td>\n

        		\n

        yok<\/b><\/span><\/p>\n<\/td>\n

        		\n

        hafif<\/b><\/span><\/p>\n<\/td>\n

        		\n

        gros 1-2*<\/b><\/span><\/p>\n<\/td>\n

        		\n

        gros 3-4*<\/b><\/span><\/p>\n<\/td>\n

        		\n

        masif*<\/b><\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

         <\/p>\n

        <\/span> <\/span> <\/span> <\/span> <\/span> <\/span> <\/span> <\/span><\/b> <\/span><\/span><\/p>\n

         <\/p>\n

        NS: normal s\u0131n\u0131rlarda, N normal<\/span><\/p>\n

         <\/p>\n

        *\u00fcnite transf\u00fczyon<\/span><\/p>\n

         <\/p>\n

        Di\u011fer T\u0131bbi \u00dcr\u00fcnler \u0130le Etkile\u015fim<\/b><\/span><\/p>\n

         <\/p>\n

        Hi\u00e7bir klinik etkile\u015fim \u00e7al\u0131\u015fmas\u0131 yap\u0131lmam\u0131\u015ft\u0131r. Kemik ili\u011fi supresyonu \u00fczerinde iyi bilinen etkileri nedeniyle, yar\u0131m v\u00fccut \u0131\u015f\u0131nlama (veya e\u015fde\u011feri), kemoterapi veya radyoaktif kemik ajanlar\u0131 (Radyum 223) ile tedavi, en az 4 hafta \u00f6ncesinden kesilmelidir.<\/span><\/p>\n

         <\/p>\n

        Dozimetri<\/b><\/span><\/p>\n

         <\/p>\n

        Lu-177 PSMA tedavisinde normal organlar i\u00e7in belirlenmi\u015f absorbe edilen spesifik doz tolerans limitleri;<\/span><\/p>\n

         <\/p>\n

          \n
        • <\/span>K\u0131rm\u0131z\u0131 kemik ili\u011fi i\u00e7in 2 Gy<\/span><\/li>\n
        • <\/span>B\u00f6brekler i\u00e7in 28-40 Gy<\/span><\/li>\n
        • <\/span>T\u00fck\u00fcr\u00fck bezi i\u00e7in 35 Gy’dir. <\/span><\/li>\n<\/ul>\n

           <\/p>\n

          Lu-177 PSMA tedavisi, \u00f6zellikle bireysel dozimetri uyguland\u0131\u011f\u0131nda standart olmayan kategoriye girer ve ulusal d\u00fczenlemelerin \u00e7o\u011fu art\u0131k bu s\u00fcre\u00e7te uzmanl\u0131k e\u011fitimi alm\u0131\u015f bir t\u0131bbi fizik uzman\u0131n\u0131n dahil edilmesini talep etmektedir. Hastalar\u0131n, dozimetri i\u00e7in gerekli olan \u00e7oklu seri g\u00f6r\u00fcnt\u00fclemeyi tolere edemedi\u011fi durumlarda, basitle\u015ftirilmi\u015f metodolojiler tercih edilebilir. Dozimetri de\u011ferlendirmeleri, gelecekteki uygulamalar\u0131n etkinli\u011fini do\u011frulamak i\u00e7in bir tedavi k\u00fcr\u00fcn\u00fcn sonras\u0131nda da yap\u0131labilir. Ancak, sonraki k\u00fcrlerde t\u00fcm\u00f6r taraf\u0131ndan absorbe edilen dozlar, ba\u015flang\u0131\u00e7 k\u00fcr\u00fcn\u00fcn\/k\u00fcrlerinin tedavi etkisiyle daha d\u00fc\u015f\u00fck olabilir. Buna kar\u015f\u0131n, normal organlardaki fizyolojik PSMA tutulumlar\u0131 tedavi k\u00fcrlerinden kayda de\u011fer etkilenmemektedir. <\/span><\/p>\n

           <\/p>\n

            \n
          • <\/span>Optimal dozimetri i\u00e7in, tercihen SPECT\/BT gibi kantitatif \u00fc\u00e7 boyutlu teknikler kullan\u0131larak birka\u00e7 zaman noktas\u0131nda ard\u0131\u015f\u0131k g\u00f6r\u00fcnt\u00fcleme yap\u0131lmal\u0131d\u0131r. Ge\u00e7 d\u00f6nemde g\u00f6r\u00fcnt\u00fcleme, organlar veya t\u00fcm\u00f6ral dokular\u0131n absorbe ettikleri dozlar\u0131 b\u00fcy\u00fck \u00f6l\u00e7\u00fcde belirledi\u011finden, taramalar uygulamadan tercihen en az 4-7 g\u00fcn sonra yap\u0131lmal\u0131d\u0131r. Organ bazl\u0131 dozimetri amac\u0131yla, doz s\u0131n\u0131rlay\u0131c\u0131 organlar i\u00e7in hastalar\u0131n her bir organ kitlesi belirlenmelidir.<\/span><\/li>\n
          • <\/span>Minimum standart, tek bir g\u00f6r\u00fcnt\u00fcleme zaman noktas\u0131nda -tercihen uygulamadan en az \u00fc\u00e7 g\u00fcn sonra- \u00fc\u00e7 boyutlu kantitatif teknikler esas al\u0131narak dozimetri hesaplanmas\u0131 \u015feklinde olmal\u0131d\u0131r. Organ bazl\u0131 dozimetri i\u00e7in, her bir hastan\u0131n organ kitleleri belirlenmeli ve efektif yar\u0131lanma \u00f6m\u00fcrleri belirtilmelidir.<\/span><\/li>\n
          • <\/span>Dozimetri yap\u0131lmad\u0131\u011f\u0131 durumlarda, k\u0131lavuzlarda verilen ortalama de\u011ferler ile b\u00f6brekler ve t\u00fck\u00fcr\u00fck bezlerinde absorbe edilen doz katsay\u0131s\u0131n\u0131n kabaca bir tahmini yap\u0131labilir. Ancak bu de\u011ferler sadece normal farmakokinetik davran\u0131\u015fta ge\u00e7erlidir; b\u00f6brek fonksiyonu bozuldu\u011funda, organlar\u0131n absorbe etti\u011fi doz da (\u00f6zellikle PSMA eksprese eden kemik lezyonlar\u0131 varl\u0131\u011f\u0131nda, k\u0131rm\u0131z\u0131 kemik ili\u011finde) \u00f6nemli \u00f6l\u00e7\u00fcde y\u00fckselebilir. Bu nedenle, bu yakla\u015f\u0131m her bir hastada tedaviyle ili\u015fkili toksisiteyi tahmin etmek i\u00e7in yeterli de\u011fildir ve toksisiteyi de\u011ferlendirmek i\u00e7in yak\u0131n takip \u00f6nerilir.<\/span><\/li>\n
          • <\/span>M\u00fcmk\u00fcn oldu\u011funda, EANM k\u0131lavuzlar\u0131na g\u00f6re ayr\u0131 ayr\u0131 t\u00fcm\u00f6r\/normal organ dozimetresi rapor edilmelidir. <\/span><\/li>\n<\/ul>\n

             <\/p>\n

            Kritik organlar i\u00e7in tahmini absorbe edilen doz katsay\u0131s\u0131lar\u0131:<\/span><\/p>\n

             <\/p>\n

              \n
            • <\/span>B\u00f6brek i\u00e7in 0.5\u00b10.2 (Gy\/GBq \u00b1 SD)<\/span><\/li>\n
            • <\/span>T\u00fck\u00fcr\u00fck bezi i\u00e7in 0.8\u00b10.5 (Gy\/GBq \u00b1 SD) \u015feklindedir. <\/span><\/li>\n<\/ul>\n

               <\/p>\n

              Radyasyon G\u00fcvenli\u011fi<\/b><\/span><\/p>\n

               <\/p>\n

              \u00c7e\u015fitli \u00e7al\u0131\u015fmalar, Lu-177 PSMA tedavisi uygulanm\u0131\u015f hastalardan; d\u0131\u015f radyasyon al\u0131m\u0131, at\u0131l\u0131m ve efektif yar\u0131lanma \u00f6mr\u00fc hakk\u0131nda veri sa\u011flamaktad\u0131r. Hastalar\u0131n tedavi uygulamas\u0131ndan en az 48 saat sonra taburcu edildi\u011fi durumlarda, tedavi ba\u015f\u0131na toplum \u00fcyelerinin maksimum efektif doz d\u00fczeyi yakla\u015f\u0131k 139 \u00b1 53 \u03bcSv d\u00fczeylerinde olmaktad\u0131r. Ancak bu veriler ayaktan tedavi uygulamalar\u0131na kolayca d\u00f6n\u00fc\u015ft\u00fcr\u00fclememektedir. Hastalar\u0131n uygulamadan 6 saat sonra taburcu edildi\u011fi, g\u00fcn\u00fc birlik tedavi uygulamalar\u0131nda ise efektif doz 202 \u00b1 43 \u03bcSv \u015feklindedir. <\/span><\/p>\n

               <\/p>\n

              Personel ve taburcu sonras\u0131 \u00f6nlemler ile ilgili olarak, n\u00f6roendokrin t\u00fcm\u00f6rlerde Lu-177 ile PRRT i\u00e7in \u00f6nerilenlerle ayn\u0131 \u00f6nlemlerin al\u0131nmas\u0131 gerekir.<\/span><\/p>\n

               <\/p>\n

              Lutesyum-177 PSMA Tedavisi Kimlere Uygulan\u0131r?<\/b><\/span><\/p>\n

               <\/p>\n

              Endikasyonlar<\/b><\/span><\/p>\n

               <\/p>\n

              Lu-177 PSMA tedavisi; metastatik, kastrasyona diren\u00e7li prostat kanseri (mCRPC) olan hastalarda a\u015fa\u011f\u0131daki durumlarda, takip eden hekimi taraf\u0131ndan tedavi amac\u0131yla \u00f6nerilebilir:<\/span><\/p>\n

               <\/p>\n

                \n
              • <\/span>Olas\u0131 tedavi se\u00e7eneklerinin t\u00fckendi\u011fi durumlarda<\/span><\/li>\n
              • <\/span>Standart alternatif tedavi se\u00e7eneklerinin uygun olmad\u0131\u011f\u0131 hastalarda<\/span><\/li>\n
              • <\/span>Tedavi \u00f6ncesi Ga-68 PSMA PET\/BT g\u00f6r\u00fcnt\u00fclemesinde, yeterli d\u00fczeyde PSMA ligand tutulumunun (uptake) g\u00f6sterildi\u011fi durumlarda<\/span><\/li>\n<\/ul>\n

                 <\/p>\n

                Ga-68 PSMA PET\/BT g\u00f6r\u00fcnt\u00fclemesi ile hastal\u0131kl\u0131 odaklar\u0131n (lezyonlar\u0131n) saptanmas\u0131 y\u00fcksek ba\u015far\u0131yla yap\u0131labilmektedir. \u015eimdiye kadar, Ga-68-PSMA-PET\/BT g\u00f6r\u00fcnt\u00fclemesinde, lezyonda hangi miktarda PSMA tutulumunun tedavi i\u00e7in yeterli olaca\u011f\u0131 konusunda, tam bir konsensus olu\u015fmam\u0131\u015ft\u0131r. Bununla birlikte, DOTA-TOC ve DOTA-TATE gibi di\u011fer teranostik ajanlardan elde edilen tecr\u00fcbeyle \u201cyeterli tutulum\u201d; en az -karaci\u011fer gibi- normal organlardaki PSMA tutulumundan daha y\u00fcksek olan d\u00fczeydir denilebilir. PSMA tedavilerinde, tedavi \u00f6ncesi Ga-68 PSMA PET\/BT g\u00f6r\u00fcnt\u00fclemelerinde, dominant t\u00fcm\u00f6r tutulum yerlerinde, PSMA maksimumSUV de\u011ferinin, karaci\u011fer ortalamaSUV de\u011ferinin en az 1,5 kat\u0131 olmas\u0131 ve PSMA tutulumu g\u00f6stermeyen aktif t\u00fcm\u00f6r dokusunun bulunmamas\u0131 gerekmektedir. Bu ama\u00e7la, PSMA ekspresyonu g\u00f6stermeyen aktif hastal\u0131\u011f\u0131n bulundu\u011fu hastalar\u0131 d\u0131\u015flamak i\u00e7in, FDG PET\/BT g\u00f6r\u00fcnt\u00fclemesi yap\u0131lmal\u0131d\u0131r. <\/span><\/p>\n

                 <\/p>\n

                Ayr\u0131ca tedavi \u00f6ncesi Ga-68 PSMA PET\/BT g\u00f6r\u00fcnt\u00fclemesinde, PSMA tutulumu g\u00f6stermeyen karaci\u011fer metastaz\u0131n\u0131n belirlendi\u011fi olgularda, di\u011fer t\u00fcm lezyonlar \u00e7ok y\u00fcksek d\u00fczeyde PSMA ekspresyonu g\u00f6sterse bile, Lu-177 PSMA tedavisi uygulanmamal\u0131d\u0131r. Bu nedenle son karar, klinik bulgulara ve g\u00f6r\u00fcnt\u00fcleme bulgular\u0131n\u0131n dikkatle de\u011ferlendirilmesine dayanmal\u0131d\u0131r.<\/span><\/p>\n

                 <\/p>\n

                Bir hastan\u0131n belirli bir alternatif tedavi i\u00e7in uygun olup olmad\u0131\u011f\u0131na ili\u015fkin karar genellikle N\u00fckleer T\u0131p Hekiminin uzmanl\u0131\u011f\u0131n\u0131n \u00f6tesindedir. Androjen yoksunlu\u011fu tedavisi (LHRH analoglar\u0131\/antagonistleri ve birinci jenerasyon antiandrojenler), ikincil hormon manip\u00fclasyonlar\u0131 (abiraterone, enzalutamide), kemoterapi veya Radyum-223 radyon\u00fcklid tedavisi a\u00e7\u0131s\u0131ndan, bir \u00fcro-\/onkolog gerekmektedir. Tedavi karar\u0131n\u0131n, \u00fcro-\/onkoloji, N\u00fckleer T\u0131p ve Radyasyon Onkolojisini i\u00e7eren multidisipliner t\u00fcm\u00f6r konseyinde de\u011ferlendirilmesi standart bir yakla\u015f\u0131m olmal\u0131 ve Lu-177 PSMA tedavisinin bireysel endikasyonu, bu multidisipliner t\u00fcm\u00f6r konseyinde kararla\u015ft\u0131r\u0131lmal\u0131d\u0131r. <\/span><\/p>\n

                 <\/p>\n

                Hastalar\u0131n kendi kaderlerini tayin etme hakk\u0131na sayg\u0131 g\u00f6sterilmeli ve hastalar, bu \u00f6nerileri kabul etmeye zorlanmamal\u0131d\u0131rlar. Her hal\u00fckarda, hastaya ilgili alandaki bir uzman (\u00f6rne\u011fin \u00fcro-\/onkolog) taraf\u0131ndan, tedavi se\u00e7eneklerinin potansiyel risk ve yararlar\u0131 hakk\u0131nda bilgi verildi\u011fi belgelenmelidir.<\/span><\/p>\n

                 <\/p>\n

                Kontraendikasyonlar<\/b><\/span><\/p>\n

                 <\/p>\n

                  \n
                • <\/span>Di\u011fer radyon\u00fcklid tedavilere benzer \u015fekilde, hayat beklentisi 6 aydan az olan olgular (ECOG performans skoru >2); ana ama\u00e7 hastal\u0131kla ili\u015fkili semptomlardan muzdarip olmak olmad\u0131k\u00e7a <\/span><\/li>\n
                • <\/span>Y\u00f6netilemeyen idrar yolu t\u0131kan\u0131kl\u0131\u011f\u0131 veya hidronefroz varl\u0131\u011f\u0131nda<\/span><\/li>\n<\/ul>\n

                   <\/p>\n

                  Bu tan\u0131 konmu\u015f veya \u00fcriner retansiyonun y\u00fcksek oldu\u011fu olgularda, ilk Lu-177 PSMA tedavisi k\u00fcr\u00fc \u00f6ncesinde mutlaka <\/span>99m<\/sup><\/span>Tc-MAG3 ya da <\/span>99m<\/sup><\/span>Tc-DTPA b\u00f6brek sintigrafisi yap\u0131lmal\u0131d\u0131r. Obstr\u00fcksiyon saptan\u0131rsa, \u00f6nce o tedavi edilmelidir. Daha sonraki k\u00fcrler \u00f6ncesinde b\u00f6brek sintigrafisi yap\u0131lmas\u0131 ise renal fonksiyonlar ve ilk b\u00f6brek sintigrafisi sonu\u00e7lar\u0131na ba\u011fl\u0131 olarak opsiyoneldir. <\/span><\/p>\n

                   <\/p>\n

                    \n
                  • <\/span>Organ fonksiyonlar\u0131nda progresif bozulma durumunda<\/span><\/li>\n<\/ul>\n

                     <\/p>\n

                    – GFR < 30 mL\/dak ve\/veya kreatinin de\u011ferinin normal \u00fcst limitin\u00a0 <\/span>>2 kat \u00fcst\u00fcnde olmas\u0131 (Bununla birlikte, diyalize ba\u011f\u0131ml\u0131 hastalara Lu-177 PSMA tedavisi uygulanabilir.)<\/span><\/p>\n

                     <\/p>\n

                    – Karaci\u011fer enzim d\u00fczeylerinin normal \u00fcst limitin >5 kat \u00fcst\u00fcnde olmas\u0131 (Karaci\u011fer metastaz\u0131 olan hastalarda, karaci\u011fer parametreleri y\u00fcksek olabilir, tek ba\u015f\u0131na bu Lu-177 PSMA tedavisi i\u00e7in bir kontrendikasyon de\u011fildir; ancak bilirubin d\u00fczeyi y\u00fcksek olan hastalarda, kolestaz d\u0131\u015flanmal\u0131 ve m\u00fcmk\u00fcnse Lu-177 PSMA tedavisinden \u00f6nce tedavi edilmelidir.)<\/span><\/p>\n

                     <\/p>\n

                      \n
                    • <\/span>Kemik ili\u011fi depresyonunda<\/span><\/li>\n<\/ul>\n

                       <\/p>\n

                      -Toplam beyaz h\u00fccre say\u0131s\u0131 < 2.5×10<\/span>9<\/sup><\/span>\/L olmas\u0131<\/span><\/p>\n

                       <\/p>\n

                      -Trombosit say\u0131s\u0131 < 75×10<\/span>9<\/sup><\/span>\/L olmas\u0131. Ancak, trombosit say\u0131s\u0131 stabil ve hastan\u0131n daha g\u00fcvenli bir tedavi se\u00e7ene\u011fi yoksa, Lu-177 PSMA tedavisi kullan\u0131labilir. Bu gibi durumlarda ilk k\u00fcrden \u00f6nce enjekte edilecek aktivite miktar\u0131n\u0131n azalt\u0131l\u0131p azalt\u0131lmayaca\u011f\u0131 ise net de\u011fildir.<\/span><\/p>\n

                       <\/p>\n

                      -Hemoglobin seviyesinin 8 g\/dL’den d\u00fc\u015f\u00fck olmas\u0131 r\u00f6latif kontrendikasyondur. Semptomatik anemi durumunda tedaviden \u00f6nce eritrosit transf\u00fczyonu yap\u0131lmal\u0131d\u0131r. Lu-177 PSMA tedavisinin kemik ili\u011finde t\u00fcm\u00f6r gerilemesi nedeniyle, kemik ili\u011fi depresyonu \u00fczerinde olumlu bir etkisi olabilir <\/span><\/p>\n

                       <\/p>\n

                      -Zaman\u0131nda m\u00fcdahale gerektiren durumlar\u0131n (radyoterapi, cerrahi) varl\u0131\u011f\u0131nda ((\u00f6rn.; spinal kord bas\u0131s\u0131 ve stabil olmayan k\u0131r\u0131klar) Lu-177 PSMA tedavisi hastan\u0131n durumuna g\u00f6re, daha sonra yap\u0131labilir. S\u0131n\u0131rda (borderline) olgular, bireysel fayda-risk de\u011ferlendirmesi a\u00e7\u0131s\u0131ndan, multidisipliner t\u00fcm\u00f6r konseyi i\u00e7inde de\u011ferlendirilmelidir.)<\/span><\/p>\n

                       <\/p>\n

                      \u25cf <\/span>\u00d6nceki miyelosupresif tedaviler (kemoterapi veya kemik hedefli radyon\u00fcklid tedavisi) PSMA tedavisinden en az 4-6 hafta \u00f6nce kesilmelidir.<\/span><\/p>\n

                       <\/p>\n

                      ECOG Performans Skalas\u0131<\/b><\/span><\/p>\n

                       <\/p>\n\n\n\n\n\n\n\n
                      \n

                      0<\/span><\/p>\n<\/td>\n

                      		\n

                      Tam aktif, hastal\u0131k \u00f6ncesi t\u00fcm aktivitelerini k\u0131s\u0131tlama olmaks\u0131z\u0131n yerine getirebilir. <\/span><\/p>\n<\/td>\n<\/tr>\n

                      \n

                      1<\/span><\/p>\n<\/td>\n

                      		\n

                      Zorlu fizik aktivitede k\u0131s\u0131tlama var, ancak ayakta ve hafif i\u015fleri yapabiliyor. \u00d6rne\u011fin; hafif ev ve ofis i\u015fleri<\/span><\/p>\n<\/td>\n<\/tr>\n

                      \n

                      2<\/span><\/p>\n<\/td>\n

                      		\n

                      Ayakta ve kendi i\u015flerini yapabiliyor, ancak herhangi bir i\u015fte \u00e7al\u0131\u015fam\u0131yor ve g\u00fcnd\u00fcz saatlerinin yar\u0131s\u0131ndan fazlas\u0131n\u0131 ayakta ge\u00e7irebiliyor.<\/span><\/p>\n<\/td>\n<\/tr>\n

                      \n

                      3<\/span><\/p>\n<\/td>\n

                      		\n

                      Kendi bak\u0131m\u0131n\u0131 yapmakta zorlan\u0131yor, g\u00fcnd\u00fcz saatlerinin yar\u0131s\u0131ndan fazlas\u0131nda yat\u0131yor veya sandalyede oturuyor.<\/span><\/p>\n<\/td>\n<\/tr>\n

                      \n

                      4<\/span><\/p>\n<\/td>\n

                      		\n

                      Kendi bak\u0131m\u0131n\u0131 yapam\u0131yor, tam olarak sandalye veya yata\u011fa ba\u011f\u0131ml\u0131.<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

                       <\/p>\n

                      <\/span><\/p>\n

                       <\/p>\n

                      Lutesyum-177 PSMA Tedavisi \u00d6ncesi Haz\u0131rl\u0131k <\/b><\/span><\/p>\n

                       <\/p>\n

                      Tedavisi planlanan hastan\u0131n N\u00fckleer T\u0131p Klini\u011fine ilk ba\u015fvurusu s\u0131ras\u0131nda a\u015fa\u011f\u0131daki bilgi ve belgeleri beraberinde getirmesi \u00f6nemlidir:<\/span><\/p>\n

                       <\/p>\n

                        \n
                      • Prostat kanseri ile ili\u015fkili en g\u00fcncel epikrizler<\/span><\/li>\n
                      • Patoloji sonu\u00e7lar\u0131 <\/span><\/li>\n
                      • Kan testleri (PSA, tam kan say\u0131m\u0131, sodyum, potasyum, fosfat, \u00fcre, kreatinin, alkalen fosfataz, albumin, AST, ALT, LDH, bilirubin, total protein, 24 saatlik idrarda kreatinin klirensi)<\/span><\/li>\n
                      • T\u00fcm v\u00fccut kemik sintigrafisi, BT, MR ve Ga-68 PSMA PET\/BT raporlar\u0131 ile orijinal film\/CD\/DVD’leri <\/span><\/li>\n<\/ul>\n

                         <\/p>\n

                        Lutesyum-177 PSMA Tedavisi Nas\u0131l Uygulan\u0131r?<\/b><\/span><\/p>\n

                         <\/p>\n

                        Tedavi Rejimleri<\/b><\/span><\/p>\n

                         <\/p>\n

                        (Lu-177 PSMA-167 ve Lu-177 PSMA-I&T ligandlar\u0131 i\u00e7in)<\/span><\/p>\n

                         <\/p>\n

                          \n
                        • Tedavi ba\u015f\u0131na uygulanan aktivite: 3,7-9,3 GBq (100\u2013250 mCi) aras\u0131ndaki g\u00f6zlemsel veri aral\u0131\u011f\u0131na dayanmaktad\u0131r. Mevcut faz II \u00e7al\u0131\u015fmalar\u0131, \u00e7o\u011fu durumda 6-8.5 GBq (160-230 mCi) standart aktiviteleri desteklemektedir. Devam eden bir faz III \u00e7al\u0131\u015fmas\u0131 (VISION) ise toplam 4 ile 6 k\u00fcrde, 6 haftal\u0131k aral\u0131klarla 7,4 GBq’lik (200 mCi) standart bir aktivite uygulamaktad\u0131r. <\/span><\/li>\n
                        • K\u00fcrler aras\u0131ndaki zaman aral\u0131\u011f\u0131 6-8 haftad\u0131r.<\/span><\/li>\n
                        • K\u00fcr say\u0131s\u0131 2 ile 6’d\u0131r (yan\u0131t, prognoz ve b\u00f6brek risk fakt\u00f6rlerine ba\u011fl\u0131 olarak de\u011fi\u015fir).<\/span><\/li>\n
                        • 1 y\u0131ldan fazla ya\u015fam beklentisi olan hastalarda, b\u00f6brek taraf\u0131ndan absorbe edilen k\u00fcm\u00fclatif doz, hasta ba\u015f\u0131na 40 Gy’i a\u015fmamal\u0131d\u0131r. Bununla birlikte, b\u00f6brekler taraf\u0131ndan absorbe edilen dozun bu s\u0131n\u0131ra yak\u0131n veya daha y\u00fcksek oldu\u011fu durumlarda, her bir hasta i\u00e7in risk\/fayda oran\u0131 mutlaka de\u011ferlendirilmelidir. K\u00fcm\u00fclatif olarak absorbe edilen maksimum doz, klinik olarak m\u00fcmk\u00fcn olan en uzun s\u00fcreye yay\u0131lmal\u0131d\u0131r.<\/span><\/li>\n
                        • Tedaviye yan\u0131t\u0131n de\u011ferlendirmesi: PSA ve tedavi sonras\u0131 sintigrafik g\u00f6r\u00fcnt\u00fcleme ile her k\u00fcrde de\u011ferlendirilmelidir. Ayr\u0131ca, her iki k\u00fcrde bir, tercihen PSMA PET\/BT olmak \u00fczere kesitsel g\u00f6r\u00fcnt\u00fclemeler ile ek evreleme \u00e7al\u0131\u015fmalar\u0131 yap\u0131lmal\u0131d\u0131r. <\/span><\/li>\n<\/ul>\n

                           <\/p>\n

                          Lu-177 PSMA’n\u0131n Uygulanmas\u0131<\/b><\/span><\/p>\n

                           <\/p>\n

                          Premedikasyon<\/i><\/b><\/span><\/p>\n

                           <\/p>\n

                          Prensip olarak Lu-177 PSMA tedavisinde, herhangi bir premedikasyona ihtiya\u00e7 yoktur.\u00a0 <\/span>\u00c7o\u011fu hasta tedaviyi iyi tolere eder. <\/span><\/p>\n

                           <\/p>\n

                          A\u015fa\u011f\u0131da Lu-177 PSMA tedavisi i\u00e7in baz\u0131 genel \u00f6neriler sunulmu\u015f olup, hastalar\u0131n bireysel durumlar\u0131 dikkate al\u0131narak uygulanmal\u0131d\u0131r:<\/span><\/p>\n

                           <\/p>\n

                            \n
                          • Ba\u011flanmam\u0131\u015f Lu-177 PSMA’n\u0131n temizlenmesini desteklemek amac\u0131yla, uygulamadan sonra di\u00fcretik kullan\u0131labilir. Dilate non-obstr\u00fcktif b\u00f6brek toplay\u0131c\u0131 sistem varl\u0131\u011f\u0131nda, Lu-177 PSMA enjeksiyonunda 30 dakika sonra, 40 mg furosemid enjeksiyonu \u00f6nerilir. Daha iyi b\u00f6brek drenaj\u0131 a\u00e7\u0131s\u0131ndan enjeksiyon sonras\u0131 hastan\u0131n oturmas\u0131 \u00f6nemlidir. <\/span><\/li>\n
                          • Her ne kadar de\u011feri tart\u0131\u015fmal\u0131 olsa da, t\u00fck\u00fcr\u00fck bezlerine, \u201ckan havuzu faz\u0131\u201d boyunca so\u011fuk paket uygulanmas\u0131, Lu-177 PSMA’n\u0131n t\u00fck\u00fcr\u00fck bezlerinde tutulumunu azaltabilir. <\/span><\/li>\n
                          • Lu-177 PSMA uygulamas\u0131 sonras\u0131 ilk 48 saatte g\u00f6r\u00fclebilecek en s\u0131k yan etki hafif mide bulant\u0131s\u0131 ve kusmad\u0131r. Bu durum Ondansetron gibi antiemetik ila\u00e7lar ile kolayca tedavi edilebilir. Yan\u0131t al\u0131namayan olgularda dimenhidrinat ya da metoklopramid yard\u0131mc\u0131 olabilir. Bununla birlikte proflaktik antiemetik tedavi t\u00fcm hastalarda zorunlu de\u011fil, opsiyoneldir.<\/span><\/li>\n
                          • Diff\u00fcz kemik ve karaci\u011fer metastaz\u0131 olan hastalar ile beyin metastaz\u0131 olan olgularda, Lu-177 PSMA uygulamas\u0131ndan 1 g\u00fcn \u00f6nce ba\u015flanarak, 1-2 hafta s\u00fcreyle, oral kortikosteroid (\u00d6rn. 20 mg\/g\u00fcn Prednizolon) kullan\u0131lmas\u0131 gerekmektedir. Di\u011fer durumlarda kullan\u0131m opsiyoneldir ve olguya ba\u011fl\u0131d\u0131r. Kortikosteroid tedavisi alan olgularda, proton pompa inhibit\u00f6rleri de proflaktik ama\u00e7l\u0131 mutlaka kullan\u0131lmal\u0131d\u0131r.\u00a0<\/span><\/li>\n<\/ul>\n

                             <\/p>\n

                            Hidrasyon ve PSMA uygulanmas\u0131<\/i><\/b><\/span><\/p>\n

                             <\/p>\n

                            Tedaviye ba\u015flamadan \u00f6nce, hastalar\u0131n bireysel kardiyovask\u00fcler ve \u00fcrinasyon ko\u015fullar\u0131na g\u00f6re I.V. veya oral hidrasyon ba\u015flat\u0131lmal\u0131d\u0131r.\u00a0<\/span><\/p>\n

                             <\/p>\n

                            Tedavi i\u00e7in, Lu-177 PSMA’n\u0131n 10-30 saniyede I.V. bolus enjeksiyonu yap\u0131l\u0131r. Al\u0131nan \u0131\u015f\u0131n\u0131n dozunu azaltmak amac\u0131yla beta radyasyonu i\u00e7in 1.5 mm pleksiglas \u015f\u0131r\u0131nga z\u0131rh\u0131, gama radyasyonu i\u00e7in kur\u015fun z\u0131rh gereklidir. <\/span><\/p>\n

                             <\/p>\n

                            D\u00fc\u015f\u00fck kardiyovask\u00fcler riski olan hastalarda, Lu-177 PSMA uygulamas\u0131n\u0131 takiben 500-2000 mL Ringer veya serum fizyolojik I.V. yoldan 20 mL\/dk ak\u0131\u015f h\u0131z\u0131nda, b\u00f6brek dozunu azaltmak i\u00e7in verilebilir. Kalp yetmezli\u011fi olan olgularda ise s\u0131v\u0131 miktar\u0131 azalt\u0131lmal\u0131d\u0131r. \u0130drar inkontinans\u0131 olan olgularda, kontaminasyonu \u00f6nlemek amac\u0131yla, 24-48 saat s\u00fcreyle idrar kateteri kullan\u0131m\u0131 tavsiye edilir.<\/span><\/p>\n

                             <\/p>\n

                            Tedavi sonras\u0131 tarama<\/i><\/b><\/span><\/p>\n

                             <\/p>\n

                            Lu-177 PSMA enjeksiyonu sonras\u0131, 4.-48. saat aras\u0131nda en az 1 t\u00fcm v\u00fccut tarama, tercihen SPECT (\/BT) yap\u0131lmal\u0131d\u0131r. Bu ama\u00e7la; medyum enerji, genel ama\u00e7l\u0131, paralel delikli kollimat\u00f6r ile 113 KeV (%20 pencere geni\u015fli\u011fi) ve 208 KeV (%15 pencere geni\u015fli\u011fi) enerji pikleri kullan\u0131lmal\u0131d\u0131r. Ac-225 PSMA uygulamas\u0131 sonras\u0131nda ise medyum enerji, genel ama\u00e7l\u0131, paralel delikli kollimat\u00f6r ve 78, 218 ve 440 KeV enerji pikleri kullan\u0131larak tedavi sonras\u0131 tarama yap\u0131labilir. <\/span><\/p>\n

                             <\/p>\n

                            PSMA tedavisinin di\u011fer tedavi se\u00e7enekleriyle kombinasyonu<\/i><\/b><\/span><\/p>\n

                             <\/p>\n

                            Lu-177 PSMA tedavisinin kemoterapi ile kombinasyonu \u00f6nerilmemektedir. Ayr\u0131ca yeni nesil hormon tedavilerine (abirateron\/enzalutamid) hala cevab\u0131 olan hastalarda her iki tedavinin kombinasyonuna ili\u015fkin veri de bulunmamaktad\u0131r. Bununla birlikte, beyin metastaz\u0131 olan hastalarda, Lu-177 PSMA tedavisi, beyin metastazlar\u0131n\u0131n eksternal radyoterapisi ile birle\u015ftirilebilir. Ayr\u0131ca bireysel deneyimler, a\u011fr\u0131l\u0131 kemik metastaz\u0131 olan veya k\u0131r\u0131lma riski olan hastalarda PSMA tedavisinin, eksternal radyoterapi ile kombinasyonun m\u00fcmk\u00fcn ve g\u00fcvenilir oldu\u011funu g\u00f6stermi\u015ftir.<\/span><\/p>\n

                             <\/p>\n

                            Takip<\/b><\/span><\/p>\n

                             <\/p>\n

                            Lu-177 PSMA tedavisine ba\u015flan\u0131lmas\u0131ndan itibaren takip muayeneleri:<\/i><\/b><\/span><\/p>\n

                             <\/p>\n

                              \n
                            • Tam kan say\u0131m\u0131; her 2-3 haftada bir (ba\u015flang\u0131\u00e7 durumuna ba\u011fl\u0131 olarak), her bir k\u00fcrden sonra 12 haftaya kadar kontrol edilmelidir.<\/span><\/li>\n
                            • T\u00fcm\u00f6r marker olarak PSA, 4 haftal\u0131k aral\u0131klarla takip edilmelidir. Takip ve yorumlamada PCWG3 (Prostat Kanseri Klinik \u00c7al\u0131\u015fmalar\u0131 \u00c7al\u0131\u015fma Grubu 3) kriterleri g\u00f6z \u00f6n\u00fcnde bulundurulmal\u0131d\u0131r. <\/span><\/li>\n
                            • Temel karaci\u011fer ve b\u00f6brek profili; her 6-8 haftada bir de\u011ferlendirilmelidir.<\/span><\/li>\n
                            • Fiziksel muayene; her tedaviden \u00f6nce yap\u0131lmal\u0131d\u0131r. <\/span><\/li>\n
                            • Tedavi sonras\u0131 tarama sintigrafisi (uygulamadan 4-48 saat sonra); hem Lu-177 PSMA’n\u0131n lezyonlarda tutulumunu teyit eder hem de daha sonraki zaman noktalar\u0131nda ger\u00e7ekle\u015ftirildi\u011finde, PSMA pozitif lezyonlar\u0131n tedaviye yan\u0131t\u0131n\u0131 g\u00f6r\u00fcnt\u00fclemede g\u00f6rev al\u0131r. <\/span><\/li>\n<\/ul>\n

                               <\/p>\n

                              Lu-177 PSMA tedavisinin birka\u00e7 k\u00fcr\u00fcnden sonra yap\u0131lacak takip muayeneleri:<\/i><\/b><\/span><\/p>\n

                               <\/p>\n

                              G\u00f6r\u00fcnt\u00fcleme tabanl\u0131 yeniden evreleme, PSMA-negatif lezyonlar\u0131n saptanmas\u0131na olanak tan\u0131mas\u0131 i\u00e7in ikinci bir g\u00f6r\u00fcnt\u00fcleme modalitesini de i\u00e7ermelidir. Bu ama\u00e7la var olan PSMA PET\/BT ya da PET\/MR incelemelerinin entegre bir par\u00e7as\u0131 olan BT ve MR g\u00f6r\u00fcnt\u00fcleri, t\u00fcm v\u00fccut kemik sintigrafisi veya FDG PET\/BT g\u00f6r\u00fcnt\u00fclemesi kullan\u0131labilir. G\u00f6r\u00fcnt\u00fcleme ile yeniden evreleme s\u0131kl\u0131\u011f\u0131, tedavi sonras\u0131 taramalar\u0131n g\u00fcvenilirli\u011fine ve PSA cevab\u0131na g\u00f6re ayarlanabilir. G\u00f6r\u00fcnt\u00fclemenin, PCWG3 kriterlerine g\u00f6re her 2-3 k\u00fcrde bir ger\u00e7ekle\u015ftirilmesi de bu ama\u00e7la makul olacakt\u0131r.<\/span><\/p>\n

                               <\/p>\n

                              Tekrar Tedavi<\/b><\/span><\/p>\n

                               <\/p>\n

                              Lu-177 PSMA tedavi s\u00fcresi, t\u00fck\u00fcr\u00fck bezleri ve b\u00f6breklerin k\u00fcm\u00fclatif absorbe etti\u011fi dozlar\u0131 dikkatlice de\u011ferlendirerek, bireysel klinik ihtiyaca g\u00f6re planlan\u0131r. Kan say\u0131m\u0131, genel t\u0131bbi durum ve dahil etme\/d\u0131\u015flama kriterleri, tekrar tedavi \u00f6ncesinde, yeniden de\u011ferlendirilmelidir. Tekrarlanan Lu-177 PSMA t<\/span>edavisi g\u00fcncel g\u00f6zlemsel \u00e7al\u0131\u015fmalarda, a\u015f\u0131r\u0131 toksisite olmaks\u0131z\u0131n, toplamda yedi k\u00fcre kadar uygulanm\u0131\u015ft\u0131r. Her 6-8 haftada bir tekrarlanan tedavi, \u00e7o\u011fu durumda hematotoksisitenin iyile\u015fmesine izin verir ve bu yay\u0131nlanm\u0131\u015f protokollerle uyumludur.<\/span><\/p>\n

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