Prostate-specific membrane antigen (PSMA), which is overexpressed in malignant prostate cancer (PCa), is an ideal target for imaging and therapy of PCa. We previously reported a PSMA imaging probe, 800CW-SCE, based on succinimidyl-Cys-C(O)-Glu (SCE) for optical imaging of PCa. In this study, we investigated the structure–activity relationships of novel SCE derivatives with five different near-infrared (NIR) fluorophores (IRDye 680LT, IRDye 750, Indocyanine Green, Cyanine 5.5, and Cyanine 7) as optical imaging probes targeting PSMA. An in vitro binding assay revealed that 800CW-SCE, 680LT-SCE, and 750-SCE exhibited higher binding affinity than 2-PMPA, which is known as a PSMA inhibitor. These three SCE derivatives were internalized into PSMA-positive cells (LNCaP cells) but not into PSMA-negative cells (PC-3 cells). In the in vivo imaging study, 800CW-SCE and 750-SCE were highly accumulated in LNCaP tumors but not in PC-3 tumors, and the ratio of LNCaP/PC-3 accumulation of 800CW-SCE was higher than that of 750-SCE. The present study may provide valuable molecular design information for the future development of new PSMA imaging probes based on the SCE scaffold.

在恶性前列腺癌（PCa）中过表达的前列腺特异性膜抗原（PSMA）是PCa成像和治疗的理想靶标。我们以前曾报道过一种基于琥珀酰亚胺基-Cys-C（O）-Glu（SCE）的PSMA成像探头800CW-SCE，用于PCa的光学成像。在这项研究中，我们研究了具有五个不同近红外（NIR）荧光团（IRDye 680LT，IRDye 750，吲哚菁绿，花菁5.5和花菁7）作为针对PSMA的光学成像探针的新型SCE衍生物的结构-活性关系。一种在体外结合测定显示800CW-SCE，680LT-SCE和750-SCE的结合亲和力比2-PMPA（称为PSMA抑制剂）的结合亲和力高。这三种SCE衍生物被内在化为PSMA阳性细胞（LNCaP细胞），而不是内化为PSMA阴性细胞（PC-3细胞）。在体内成像研究中，LNCaP肿瘤中高度积累了800CW-SCE和750-SCE，而PC-3肿瘤中却没有积累800CW-SCE和800CW-SCE的LNCaP / PC-3积累的比率高于750-SCE 。本研究可能为基于SCE支架的新型PSMA成像探针的未来开发提供有价值的分子设计信息。