Department of Radiology, Biomedical Research Imaging Center, and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Mol Pharm. 2022 Feb 7;19(2):720-727. doi: 10.1021/acs.molpharmaceut.1c00743. Epub 2021 Dec 22.
Radiolabeled prostate-specific membrane antigen (PSMA) ligands have been rapidly adopted as part of patient care for prostate cancer. In this study, a new series of F-labeled PSMA-targeting agents was developed based on the high-affinity Glu-ureido-Lys scaffold and F-vinyl sulfones (VSs), the tumor uptake and tumor/major organ contrast of which could be tuned by pharmacokinetic linkers within the molecules. In particular, F-PEG-VS-PSMAi showed the highest tumor uptake (12.1 ± 2.2%ID/g at 0.5 h p.i.) and F-PEG-VS-PSMAi showed the highest tumor-to-liver ratio (T/L = 3.7 ± 1.0, 4.8 ± 1.2, and 6.3 ± 1.1 at 0.5, 1.5, and 3 h p.i. respectively). Significantly, compared with the FDA-approved Ga-PSMA-11, the newly developed F-PEG-VS-PSMAi has an almost double tumor uptake ( < 0.0001) when tested in the same animal model. In conclusion, F-VS-labeled PSMA ligands are promising PET agents with prominent tumor uptake and high contrast. The lead agents F-PEG-VS-PSMAi and F-PEG-VS-PSMAi warrant further evaluation in prostate cancer patients.
放射性标记的前列腺特异性膜抗原（PSMA）配体已迅速被采用为前列腺癌患者治疗的一部分。在这项研究中，基于高亲和力的 Glu-ureido-Lys 支架和 F-乙烯砜（VS），开发了一系列新的 F 标记的 PSMA 靶向试剂，其分子内的药代动力学连接子可以调节肿瘤摄取和肿瘤/主要器官对比。特别是，F-PEG-VS-PSMAi 显示出最高的肿瘤摄取（0.5 h p.i.时为 12.1 ± 2.2%ID/g），F-PEG-VS-PSMAi 显示出最高的肿瘤与肝脏的比值（T/L = 3.7 ± 1.0、4.8 ± 1.2 和 6.3 ± 1.1，分别在 0.5、1.5 和 3 h p.i.时）。值得注意的是，与 FDA 批准的 Ga-PSMA-11 相比，当在相同的动物模型中进行测试时，新开发的 F-PEG-VS-PSMAi 的肿瘤摄取几乎增加了一倍（<0.0001）。总之，F-VS 标记的 PSMA 配体是有前途的 PET 试剂，具有突出的肿瘤摄取和高对比度。先导试剂 F-PEG-VS-PSMAi 和 F-PEG-VS-PSMAi 值得在前列腺癌患者中进一步评估。
