Alpha- versus beta-particle radiopeptide therapy in a human prostate cancer model (²¹³Bi-DOTA-PESIN and ²¹³Bi-AMBA versus ¹⁷⁷Lu-DOTA-PESIN)

Recurrent prostate cancer presents a challenge to conventional treatment, particularly so to address micrometastatic and small-volume disease. Use of α-radionuclide therapy is considered as a highly effective treatment in such applications due to the shorter range and exquisite cytotoxicity of α-particles as compared with β-particles. ²¹³Bi is considered an α-emitter with high clinical potential, due to its short half-life (45.6 minutes) being well matched for use in peptide-receptor radionuclide α-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-CH ₂CO-8-aminooctanoyl-Q-W-A-V-G-H-L-M-NH₂ (AMBA), were compared with ¹⁷⁷Lu (β-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 β-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 α-therapy treating. recurrent prostate cancer.