An Alpha-Particle Emiting Radiopeptide (213 Bi-DOTA-PESIN) for Therapy of Prostate Cancer

Recurrent prostate cancer presents a challenge to conventional treatment, particularly so to address micrometastatic and small-volume disease. Use of a-radionuclide therapy is considered as a highly effective treatment in such applications due to the shorter range and exquisite cytotoxicity of a-particles as compared with b-particles. 213Bi is considered an a-emitter with high clinical potential, due to its short half-life (45.6 minutes) being well matched for use in peptide-receptor radionuclide a-therapy; however, there is limited knowledge available within this context of use. In this study, two novel 213Bi-labeled peptides, DOTA-PEG4- bombesin (DOTA-PESIN) and DO3A-CH2CO-8-aminooctanoyl-Q-W-A-V-G-H-L-M-NH2 (AMBA), were compared with 177Lu (b-emitter)-labeled DOTA-PESIN in a human androgen-independent prostate carcinoma xenograft model (PC-3 tumor). Animals were injected with 177Lu-DOTA-PESIN, 213Bi-DOTA-PESIN, or 213Bi- AMBA to determine the maximum tolerated dose (MTD), biodistribution, and dosimetry of each agent; controls were left untreated or were given nonradioactive 175Lu-DOTA-PESIN. The MTD of 213Bi-DOTA-PESIN and 213Bi- AMBA was 25 MBq (0.68 mCi) whereas 177Lu-DOTA-PESIN showed an MTD of 112 MBq (3 mCi). At these dose levels, 213Bi-DOTA-PESIN and 213Bi-AMBA were significantly more effective than 177Lu-DOTA-PESIN. At the same time, 177Lu-DOTA-PESIN showed minimal, 213Bi-DOTA-PESIN slight, and 213Bi-AMBA marked kidney damage 20 to 30 weeks posttreatment. These preclinical data indicate that a-therapy with 213Bi-DOTA-PESIN or 213Bi-AMBA is more efficacious than b-therapy. Furthermore, 213Bi-DOTA-PESIN has a better safety profile than 213Bi-AMBA, and represents a possible new approach for use in peptide-receptor radionuclide a-therapy treating recurrent prostate cancer.

WILD D.;  FRISCHKNECHT M.;  ZHANG H.;  MORGENSTERN Alfred;  BRUCHERTSEIFER Frank;  BOISCLAIR J.;  PROVENCHER-BOLLIGER A.;  REUBI Jean-Claude;  MAECKE H. R.; 

2011-10-20

AMER ASSOC CANCER RESEARCH

JRC54279

0008-5472,   

http://cancerres.aacrjournals.org/content/71/3/1009.full.pdf,    html,    https://publications.jrc.ec.europa.eu/repository/handle/JRC54279,   

10.1158/0008-5472.CAN-10-1186,