⁶⁸Ga-radiolabeled small molecules that specifically target prostate-specific membrane antigen (PSMA) have been extensively investigated, and some of these tracers have been used in the diagnosis of prostate cancer via ⁶⁸Ga-positron emission tomography (⁶⁸Ga-PET). Nevertheless, current ⁶⁸Ga-labeled radiotracers show only fair detection rates for metastatic prostate cancer lesions, especially those with lower levels of prostate specific antigen (PSA), which often occurs in the biochemical recurrence of prostate cancer. The goal of this study was to design and synthesize a new PSMA-targeted radiotracer, ⁶⁸Ga-SC691, with high affinity for prostate cancer cells and excellent pharmacokinetics. To this end, structural optimization was carried out on the bifunctional group, target motif, and linker while the high affinity targeting scaffold remained. To explore its potential in the clinic, a comparative study was further performed in vitro and in vivo between ⁶⁸Ga-SC691 and ⁶⁸Ga-PSMA-11, a clinically approved tracer for PSMA-positive prostate cancer. SC691 was radiolabeled to provide ⁶⁸Ga-SC691 in 99% radiolabeling yield under mild conditions. High uptake and a high internalization ratio into LNCaP cells were observed in in vitro studies. In vivo studies showed that ⁶⁸Ga-SC691 had favorable biodistribution properties and could specifically accumulate on PSMA-positive LNCaP xenografts visualized by micro-PET/CT. This radiotracer showed excellent PET imaging quality and comparable, if not higher, uptake in LNCaP xenografts than ⁶⁸Ga-PSMA-11.

⁶⁸ Ga 放射性标记的小分子专门针对前列腺特异性膜抗原 (PSMA) 已得到广泛研究，其中一些示踪剂已通过⁶⁸ Ga 正电子发射断层扫描 ( ⁶⁸ Ga-PET)用于诊断前列腺癌。尽管如此，目前⁶⁸ Ga 标记的放射性示踪剂对转移性前列腺癌病变的检出率只有一般，尤其是那些前列腺特异性抗原 (PSA) 水平较低的病变，这通常发生在前列腺癌的生化复发中。这项研究的目标是设计和合成一种新的 PSMA 靶向放射性示踪剂，⁶⁸Ga-SC691，对前列腺癌细胞具有高亲和力和优异的药代动力学。为此，在保留高亲和力靶向支架的同时，对双功能基团、目标基序和接头进行了结构优化。为了探索其在临床中的潜力，在⁶⁸ Ga-SC691 和⁶⁸ Ga-PSMA-11（一种临床批准的 PSMA 阳性前列腺癌示踪剂）之间进一步进行了体外和体内比较研究。SC691 被放射性标记以在温和条件下以 99% 的放射性标记产率提供⁶⁸ Ga-SC691。在体外研究中观察到 LNCaP 细胞的高摄取和高内化率。体内研究表明，⁶⁸Ga-SC691 具有良好的生物分布特性，可以在微 PET/CT 显示的 PSMA 阳性 LNCaP 异种移植物上特异性积累。这种放射性示踪剂显示出出色的 PET 成像质量，并且与⁶⁸ Ga-PSMA-11相比，LNCaP 异种移植物的吸收即使不是更高，也是相当的。