Pan Donghui, Yan Yongjun, Yang Ronghua, Xu Yu Ping, Chen Fei, Wang Lizhen, Luo Shineng, Yang Min
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, 214063, China.
Contrast Media Mol Imaging. 2014 Sep-Oct;9(5):342-8. doi: 10.1002/cmmi.1583. Epub 2014 Apr 14.
Overexpression of the gastrin-releasing peptide receptor (GRPR) in prostate cancer provides a promising target for detection the disease. MATBBN is a new bombesin analog originating from the GRPR antagonists with a hydrophilic linker. In this study NOTA-conjugated MATBBN was labeled by the Al(18)F method and the potential of (18)F-Al-NOTA-MATBBN for prostate tumor PET imaging was also evaluated. NOTA-MATBBN was radiolabeled with (18) F using Al(18)F complexes. Partition coefficient, in vitro stability and GRPR binding affinity were also determined. PET studies were performed with (18)F-Al-NOTA-MATBBN in PC-3 tumor-bearing mice. (18)F-Al-NOTA-MATBBN can be produced within 30 min with a decay-corrected yield of 62.5 ± 2.1% and a radiochemical purity of >98%. The logP octanol-water value for the Al(18)F-labeled BBN analog was -2.40 ± 0.07 and the radiotracer was stable in phosphate-buffered saline and human serum for 2 h. The IC50 values of displacement for the (18)F-Al-NOTA-MATBBN with MATBBN was 126.9 ± 2.75 nm. The PC-3 tumors were clearly visible with high contrast after injection of the labeled peptide. At 60 min post-injection, the tumor uptakes for (18)F-Al-NOTA-MATBBN and (18)F-FDG were 4.59 ± 0.43 and 1.98 ± 0.35% injected dose/g, and tumor to muscle uptake radios for two tracers were 6.77 ± 1.10 and 1.78 ± 0.32, respectively. Dynamic PET revealed that (18) F-Al-NOTA-MATBBN was excreted mainly through the kidneys. GRPR-binding specificity was also demonstrated by reduced tumor uptake of (18)F-Al-NOTA-MATBBN after coinjection with excess unlabeled MATBBN peptide at 1 h post-injection. NOTA- MATBBN could be labeled rapidly with (18)F using one step method. (18)F-Al-NOTA-MATBBN may be a promising PET imaging agent for prostate cancer.
胃泌素释放肽受体（GRPR）在前列腺癌中的过表达为该疾病的检测提供了一个有前景的靶点。MATBBN是一种新的蛙皮素类似物，源自带有亲水性连接体的GRPR拮抗剂。在本研究中，NOTA偶联的MATBBN通过Al(18)F法进行标记，并且还评估了(18)F-Al-NOTA-MATBBN用于前列腺肿瘤PET成像的潜力。NOTA-MATBBN使用Al(18)F络合物用(18)F进行放射性标记。还测定了分配系数、体外稳定性和GRPR结合亲和力。用(18)F-Al-NOTA-MATBBN在荷PC-3肿瘤的小鼠中进行PET研究。(18)F-Al-NOTA-MATBBN可在30分钟内产生，衰变校正产率为62.5±2.1%，放射化学纯度>98%。Al(18)F标记的BBN类似物的辛醇-水logP值为-2.40±0.07，放射性示踪剂在磷酸盐缓冲盐水和人血清中2小时内稳定。(18)F-Al-NOTA-MATBBN与MATBBN的置换IC50值为126.9±2.75nm。注射标记肽后，PC-3肿瘤以高对比度清晰可见。注射后60分钟，(18)F-Al-NOTA-MATBBN和(18)F-FDG的肿瘤摄取量分别为4.59±0.43和1.98±0.35%注射剂量/克，两种示踪剂的肿瘤与肌肉摄取比分别为6.77±1.10和1.78±0.32。动态PET显示(18)F-Al-NOTA-MATBBN主要通过肾脏排泄。在注射后1小时与过量未标记的MATBBN肽共同注射后，(18)F-Al-NOTA-MATBBN的肿瘤摄取减少，也证明了GRPR结合特异性。NOTA-MATBBN可以用一步法快速用(18)F进行标记。(18)F-Al-NOTA-MATBBN可能是一种有前景的前列腺癌PET成像剂。
