The gastrin-releasing peptide receptor (GRPR) is overexpressed in prostate cancer and other solid malignancies. Following up on our work on [68Ga]Ga-ProBOMB1 that had better imaging characteristics than [68Ga]Ga-NeoBOMB1, we investigated the effects of substituting 68Ga for 177Lu to determine if the resulting radiopharmaceuticals could be used with a therapeutic aim. We radiolabeled the bombesin antagonist ProBOMB1 (DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-ψ-Pro-NH2) with lutetium-177 and compared it with [177Lu]Lu-NeoBOMB1 (obtained in 54.2 ± 16.5 % isolated radiochemical yield with > 96% radiochemical purity and 440.8 ± 165.1 GBq/μmol molar activity) for GRPR targeting. Lu-NeoBOMB1 had better binding affinity for GRPR than Lu-ProBOMB1(Ki values: 2.26 ± 0.24 and 30.2 ± 3.23 nM). [177Lu]Lu-ProBOMB1 was obtained in 53.7 ± 5.4% decay-corrected radiochemical yield with 444.2 ± 193.2 GBq/μmol molar activity, and > 95% radiochemical purity. In PC-3 prostate cancer xenograft mice, tumor uptake of [177Lu]Lu-ProBOMB1 was 3.38 ± 1.00, 1.32 ± 0.24, and 0.31 ± 0.04 %ID/g at 1, 4 and 24 h p.i. However, the uptake in tumor was lower than [177Lu]Lu-NeoBOMB1 at all time points. [177Lu]Lu-ProBOMB1 was inferior to [177Lu]Lu-NeoBOMB1, which had better therapeutic index for the organs receiving the highest doses.

中文翻译：

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[177 Lu]Lu-ProBOMB1 和 [177 Lu]Lu-NeoBOMB1 用于 GRPR 靶向的生物学特性比较

胃泌素释放肽受体 (GRPR) 在前列腺癌和其他实体恶性肿瘤中过度表达。继我们对具有比 [68Ga]Ga-NeoBOMB1 更好成像特性的 [68Ga]Ga-ProBOMB1 的研究之后，我们研究了用 68Ga 代替 177Lu 的效果，以确定所得放射性药物是否可用于治疗目的。我们用 lutetium-177 对铃蟾肽拮抗剂 ProBOMB1 (DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-ψ-Pro-NH2) 进行放射性标记，并将其与 [177Lu]Lu- NeoBOMB1（以 54.2 ± 16.5 % 的分离放射化学产率获得，放射化学纯度 > 96%，摩尔活性为 440.8 ± 165.1 GBq/μmol），用于 GRPR 靶向。Lu-NeoBOMB1 对 GRPR 的结合亲和力比 Lu-ProBOMB1 更好（Ki 值：2.26 ± 0.24 和 30.2 ± 3.23 nM）。[177Lu]Lu-ProBOMB1 在 53.7 ± 5 中获得。4% 衰减校正的放射化学产率，摩尔活性为 444.2 ± 193.2 GBq/μmol，放射化学纯度 > 95%。在 PC-3 前列腺癌异种移植小鼠中，[177Lu]Lu-ProBOMB1 的肿瘤摄取在注射后 1、4 和 24 小时分别为 3.38 ± 1.00、1.32 ± 0.24 和 0.31 ± 0.04 %ID/g。在所有时间点均低于 [177Lu]Lu-NeoBOMB1。[177Lu]Lu-ProBOMB1不如[177Lu]Lu-NeoBOMB1，后者对接受最高剂量的器官具有更好的治疗指数。