Recently, promising results of antitumor activity were observed in patients with metastatic castration resistant prostate cancer treated with [177Lu]Lu-PSMA. Radionuclide therapy efficacy may even be improved by using the alpha emitter Ac-225. Higher efficacy is claimed due to high LET energies specifically towards PSMA positive cells, causing more double strand breaks. The aim of this study is to manufacture [225Ac]Ac-PSMA-I&T according to good manufacturing practice guidelines for the translation of [225Ac]Ac-PSMA-I&T into the clinic for phase 1 dose escalation study. For labeling and optimization, quencher addition during labeling is investigated. Quality control of [225Ac]Ac-PSMA-I&T is based on measurement of Fr-221 (218KeV), which forms an equilibrium with Ac-225 in ~6T½ of Fr-221 (4.8min). Radio-(I)TLC methods are utilized for identification of the different chemical forms, gamma-counter for concentration determination, and radiochemical yield by HPGe-detector. Radiochemical purity is determined by HPLC analyzes. Final patient dose is prepared and diluted with equal ratio quencher as during labeling with an activity of 8-12MBq(±5%), pH>5.5, 100μg(±20%)PSMA-I&T, radiochemical yield >95%, radiochemical purity >90% (up to 3h after filtration), endotoxin levels of <5EU/mL, osmolarity of 2100 mOsmol and produced according to current guidelines. The start of phase I dose escalation study is planned in the near future.

HOOIJMAN Eline;  CHALISKAN Yoslem;  LING S W;  KARYGAHIL Figen;  SEGBERS Marcel;  BRUCHERTSEIFER Frank;  MORGENSTERN Alfred;  SEIMBILLE Yann;  KOOLEN Stijn;  BRABANDER Tessa;  DE BLOIS Erik; 

2021-05-27

MDPI

JRC124591

1999-4923 (online),   

https://publications.jrc.ec.europa.eu/repository/handle/JRC124591,   

10.3390/pharmaceutics13050715 (online),