Division of Radiological Chemistry, University Hospital, Basel, Switzerland.
Cancer Res. 2011 Feb 1;71(3):1009-18. doi: 10.1158/0008-5472.CAN-10-1186. Epub 2011 Jan 18.
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. (213)Bi 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 (213)Bi-labeled peptides, DOTA-PEG(4)-bombesin (DOTA-PESIN) and DO3A-CH(2)CO-8-aminooctanoyl-Q-W-A-V-G-H-L-M-NH(2) (AMBA), were compared with (177)Lu (β-emitter)-labeled DOTA-PESIN in a human androgen-independent prostate carcinoma xenograft model (PC-3 tumor). Animals were injected with (177)Lu-DOTA-PESIN, (213)Bi-DOTA-PESIN, or (213)Bi-AMBA to determine the maximum tolerated dose (MTD), biodistribution, and dosimetry of each agent; controls were left untreated or were given nonradioactive (175)Lu-DOTA-PESIN. The MTD of (213)Bi-DOTA-PESIN and (213)Bi-AMBA was 25 MBq (0.68 mCi) whereas (177)Lu-DOTA-PESIN showed an MTD of 112 MBq (3 mCi). At these dose levels, (213)Bi-DOTA-PESIN and (213)Bi-AMBA were significantly more effective than (177)Lu-DOTA-PESIN. At the same time, (177)Lu-DOTA-PESIN showed minimal, (213)Bi-DOTA-PESIN slight, and (213)Bi-AMBA marked kidney damage 20 to 30 weeks posttreatment. These preclinical data indicate that α-therapy with (213)Bi-DOTA-PESIN or (213)Bi-AMBA is more efficacious than β-therapy. Furthermore, (213)Bi-DOTA-PESIN has a better safety profile than (213)Bi-AMBA, and represents a possible new approach for use in peptide-receptor radionuclide α-therapy treating recurrent prostate cancer.
复发性前列腺癌对传统治疗构成挑战，尤其是对于微转移和小体积疾病的治疗更是如此。与β粒子相比，α放射性核素治疗由于α粒子的射程更短和细胞毒性更高，因此被认为是一种非常有效的治疗方法。(213)Bi 被认为是一种具有高临床潜力的α发射体，因为其半衰期（45.6 分钟）非常适合用于肽受体放射性核素α治疗；然而，在这种使用情况下，相关知识有限。在这项研究中，两种新型的(213)Bi 标记肽，DOTA-PEG(4)-bombesin (DOTA-PESIN) 和 DO3A-CH(2)CO-8-氨基辛酰基-Q-W-A-V-G-H-L-M-NH(2) (AMBA)，与(177)Lu（β发射器）标记的 DOTA-PESIN 在人雄激素非依赖性前列腺癌异种移植模型（PC-3 肿瘤）中进行了比较。动物注射(177)Lu-DOTA-PESIN、(213)Bi-DOTA-PESIN 或(213)Bi-AMBA 以确定每种药物的最大耐受剂量 (MTD)、生物分布和剂量学；对照组未接受治疗或给予非放射性 (175)Lu-DOTA-PESIN。(213)Bi-DOTA-PESIN 和(213)Bi-AMBA 的 MTD 为 25MBq（0.68mCi），而(177)Lu-DOTA-PESIN 的 MTD 为 112MBq（3mCi）。在这些剂量水平下，(213)Bi-DOTA-PESIN 和(213)Bi-AMBA 比(177)Lu-DOTA-PESIN 更有效。与此同时，(177)Lu-DOTA-PESIN 显示出最小的、(213)Bi-DOTA-PESIN 轻微的和(213)Bi-AMBA 明显的肾脏损伤，在治疗后 20 至 30 周。这些临床前数据表明，(213)Bi-DOTA-PESIN 或(213)Bi-AMBA 的α治疗比β治疗更有效。此外，(213)Bi-DOTA-PESIN 的安全性优于(213)Bi-AMBA，为肽受体放射性核素α治疗复发性前列腺癌提供了一种新的可能方法。
