Guo Yirui, Gao Dingyao, Chen Yinfei, Zhang Yu, Chen Liping, Mao Yong, Yu Chunjing, Qiu Ling, Lin Jianguo
Wuxi School of Medicine, Jiangnan University, Wuxi 214122, P. R. China.
NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, P. R. China.
ACS Omega. 2021 Mar 17;6(12):8279-8287. doi: 10.1021/acsomega.0c06353. eCollection 2021 Mar 30.
Prostate-specific membrane antigen (PSMA) is a prospect biomarker for the treatment of prostate cancer. Meanwhile, positron emission tomography (PET) is being developed as a significant imaging modality in cancer diagnosis. A new PET probe Glu-ureido-Lys-naphthylalanine-tranexamic acid-Gly(AMBF)-triiodobenzoic acid (F-GLNTGT) was radiosynthesized by a one-step F-labeled method. F-GLNTGT was obtained with a radioactivity yield (RCY) of 12.16 ± 6.4% and a good radiochemical purity (RCP > 96%). The cell uptakes of F-GLNTGT were determined to be 15.9 ± 0.43% ID and 9.47 ± 1.26% ID at 15 min in LNCaP cells and PC-3 cells, respectively. The cell internalization of F-GLNTGT was determined to be 12.89 ± 0.94% ID and 5.34 ± 0.15% ID at 15 min in LNCaP cells and PC-3 cells, respectively. It is suggested that the probe has good specificity targeting PSMA. From the results of F-GLNTGT binding affinity with PSMA, it has a higher affinity and a value of 0.49 nM (95% confidence interval (CI): 0.35-0.67 nM). In PET imaging, F-GLNTGT showed the highest tumor uptake of 3.51 ± 0.15% ID/g at 45 min and the maximum tumor/muscle (T/M) ratio of 3.68 ± 0.29 at 60 min post-injection (p.i.) in LNCaP tumors. The control probe F-AlF-NOTA-RGD presented the highest tumor uptake of 4.2 ± 0.54% ID/g at 7.5 min and the T/M ratio of 2.72 ± 0.63 at 45 min p.i. in LNCaP tumors. The results showed that the probe has a higher tumor/muscle ratio compared with the control probe F-AlF-NOTA-RGD. Although the probe F-GLNTGT has some limitations for CT signal detection both in cells and , it is still a promising PET probe for targeting PSMA membrane protein.
前列腺特异性膜抗原（PSMA）是前列腺癌治疗的一种潜在生物标志物。同时，正电子发射断层扫描（PET）正发展成为癌症诊断中的一种重要成像方式。一种新的PET探针Glu-脲基-Lys-萘丙氨酸-氨甲环酸-Gly(AMBF)-三碘苯甲酸（F-GLNTGT）通过一步法F标记进行放射性合成。F-GLNTGT的放射性产率（RCY）为12.16±6.4%，放射化学纯度良好（RCP>96%）。F-GLNTGT在LNCaP细胞和PC-3细胞中15分钟时的细胞摄取量分别测定为15.9±0.43%ID和9.47±1.26%ID。F-GLNTGT在LNCaP细胞和PC-3细胞中15分钟时的细胞内化量分别测定为12.89±0.94%ID和5.34±0.15%ID。提示该探针具有良好的靶向PSMA的特异性。从F-GLNTGT与PSMA的结合亲和力结果来看，它具有较高的亲和力，解离常数（KD）值为0.49 nM（95%置信区间（CI）：0.35 - 0.67 nM）。在PET成像中，F-GLNTGT在LNCaP肿瘤中注射后（p.i.)45分钟时肿瘤摄取率最高，为3.51±0.15%ID/g，60分钟时肿瘤/肌肉（T/M）比值最大，为3.68±0.29。对照探针F-AlF-NOTA-RGD在LNCaP肿瘤中注射后7.5分钟时肿瘤摄取率最高，为4.2±0.54%ID/g；45分钟时T/M比值为2.72±0.63。结果表明，与对照探针F-AlF-NOTA-RGD相比，该探针具有更高的肿瘤/肌肉比值。尽管探针F-GLNTGT在细胞和体内CT信号检测方面存在一些局限性，但它仍是一种有前景的靶向PSMA膜蛋白的PET探针。
