Lu-DOTA-PESIN ) 177 Bi-AMBA versus 213 Bi-DOTA-PESIN and 213 Human Prostate Cancer Model ( Alpha-versus Beta-Particle Radiopeptide Therapy in a Updated

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. Bi 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 Bi-labeled peptides, DOTA-PEG4bombesin (DOTA-PESIN) and DO3A-CH2CO-8-aminooctanoyl-Q-W-A-V-G-H-L-M-NH2 (AMBA), were compared with Lu (b-emitter)-labeled DOTA-PESIN in a human androgen-independent prostate carcinoma xenograft model (PC-3 tumor). Animals were injected with Lu-DOTA-PESIN, Bi-DOTA-PESIN, or BiAMBA to determine the maximum tolerated dose (MTD), biodistribution, and dosimetry of each agent; controls were left untreated or were given nonradioactive Lu-DOTA-PESIN. The MTD of Bi-DOTA-PESIN and BiAMBA was 25 MBq (0.68 mCi) whereas Lu-DOTA-PESIN showed an MTD of 112 MBq (3 mCi). At these dose levels, Bi-DOTA-PESIN and Bi-AMBA were significantly more effective than Lu-DOTA-PESIN. At the same time, Lu-DOTA-PESIN showed minimal, Bi-DOTA-PESIN slight, and Bi-AMBA marked kidney damage 20 to 30 weeks posttreatment. These preclinical data indicate that a-therapy with Bi-DOTA-PESIN or Bi-AMBA is more efficacious than b-therapy. Furthermore, Bi-DOTA-PESIN has a better safety profile than Bi-AMBA, and represents a possible new approach for use in peptide-receptor radionuclide a-therapy treating recurrent prostate cancer. Cancer Res; 71(3); 1009–18. 2011 AACR.