Pourghiasian Maral, Liu Zhibo, Pan Jinhe, Zhang Zhengxing, Colpo Nadine, Lin Kuo-Shyan, Perrin David M, Bénard François
Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
Chemistry Department, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada.
Bioorg Med Chem. 2015 Apr 1;23(7):1500-6. doi: 10.1016/j.bmc.2015.02.009. Epub 2015 Feb 20.
A novel radiofluorinated derivative of bombesin, (18)F-AmBF3-MJ9, was synthesized and evaluated for its potential to image prostate cancer by targeting the gastrin releasing peptide receptor (GRPR). AmBF3-MJ9 was prepared from an ammoniomethyl-trifluoroborate (AmBF3) conjugated alkyne 2 and azidoacetyl-MJ9 via a copper-catalyzed click reaction, and had good binding affinity for GRPR (Ki=0.5±0.1nM). The (18)F-labeling was performed via a facile one-step (18)F-(19)F isotope exchange reaction, and (18)F-AmBF3-MJ9 was obtained in 23±5% (n=3) radiochemical yield in 25min with >99% radiochemical purity and 100±32GBq/μmol specific activity. (18)F-AmBF3-MJ9 was stable in mouse plasma, and was partially (22-30%) internalized after binding to GRPR. Positron emission tomography (PET) imaging and biodistribution studies in mice showed fast renal excretion and good uptake of (18)F-AmBF3-MJ9 by GRPR-expressing pancreas and PC-3 prostate cancer xenografts. Tumor uptake was 1.37±0.25%ID/g at 1h, and 2.20±0.13%ID/g at 2h post-injection (p.i.) with low background uptake and excellent tumor visualization (tumor-to-muscle ratios of 75.4±5.5). These data suggest that (18)F-AmBF3-MJ9 is a promising PET tracer for imaging GRPR-expressing prostate cancers.
合成了一种新型的蛙皮素放射性氟化衍生物(18)F-AmBF3-MJ9，并评估了其通过靶向胃泌素释放肽受体(GRPR)对前列腺癌进行成像的潜力。AmBF3-MJ9由氨甲基三氟硼酸盐(AmBF3)共轭炔烃2和叠氮乙酰-MJ9通过铜催化的点击反应制备而成，对GRPR具有良好的结合亲和力(Ki=0.5±0.1nM)。(18)F标记通过简便的一步(18)F-(19)F同位素交换反应进行，在25分钟内以23±5%(n=3)的放射化学产率获得(18)F-AmBF3-MJ9，放射化学纯度>99%，比活度为100±32GBq/μmol。(18)F-AmBF3-MJ9在小鼠血浆中稳定，与GRPR结合后部分(22-30%)被内化。小鼠的正电子发射断层扫描(PET)成像和生物分布研究表明，(18)F-AmBF3-MJ9经肾脏快速排泄，表达GRPR的胰腺和PC-3前列腺癌异种移植瘤对其摄取良好。注射后1小时肿瘤摄取为1.37±0.25%ID/g，2小时时为2.20±0.13%ID/g，背景摄取低，肿瘤可视化效果极佳(肿瘤与肌肉的比值为75.4±5.5)。这些数据表明，(18)F-AmBF3-MJ9是一种有前景的PET示踪剂，可用于对表达GRPR的前列腺癌进行成像。
