前列腺特异性膜抗原（PSMA）是前列腺癌的理想靶向物质，可用于显像和放射性核素治疗。最近，[177Lu]Lu-PSMA-617（Pluvicto）获得了FDA的放射性核素治疗批准。为了开发同时靶向PSMA和骨转移的异二价剂，我们制备了[177Lu]Lu-P17-079（[177Lu]Lu-1）和[177Lu]Lu-P17-081（[177Lu]Lu-2）。对PC3-PIP（PSMA阳性）肿瘤携带的小鼠进行的体内分布研究显示，[177Lu]Lu-PSMA-617、[177Lu]Lu-1和[177Lu]Lu-2在PSMA阳性肿瘤中的摄取率较高（分别为1小时时的14.5％、14.7％和11.3％ID/g），骨摄取率差异明显（分别为1小时时的0.52％、6.52％和5.82％ID/g）。在相同的小鼠模型中，使用[68Ga]Ga-P17-079（[68Ga]Ga-1）进行PET显像显示出优异的图像，证实了期望的双重靶向PSMA阳性肿瘤和骨。研究结果表明，[177Lu]Lu-P17-079（[177Lu]Lu-1）是进一步开发的有前景的异二价放射性核素治疗药物候选物，可同时靶向PSMA表达和前列腺癌骨转移的治疗。

Prostate-specific membrane antigen (PSMA) is an excellent target for imaging and radionuclide therapy of prostate cancer. Recently, [177Lu]Lu-PSMA-617 (Pluvicto) was approved by the FDA for radionuclide therapy. To develop hetero-bivalent agents targeting both PSMA and bone metastasis, [177Lu]Lu-P17-079 ([177Lu]Lu-1) and [177Lu]Lu-P17-081 ([177Lu]Lu-2) were prepared. In vivo biodistribution studies of [177Lu]Lu-PSMA-617, [177Lu]Lu-1, and [177Lu]Lu-2 in mice bearing PC3-PIP (PSMA positive) tumor showed high uptake in PSMA-positive tumor (14.5, 14.7, and 11.3% ID/g at 1 h, respectively) and distinctively different bone uptakes (0.52, 6.52, and 5.82% ID/g at 1 h, respectively). PET imaging using [68Ga]Ga-P17-079 ([68Ga]Ga-1) in the same mouse model displayed excellent images confirming the expected dual-targeting to PSMA-positive tumor and bone. Results suggest that [177Lu]Lu-P17-079 ([177Lu]Lu-1) is a promising candidate for further development as a hetero-bivalent radionuclide therapy agent targeting both PSMA expression and bone metastases for the treatment of prostate cancer.