A Preclinical Study on GRPR-Targeted 68Ga-Probes for PET Imaging of Prostate Cancer

Gastrin-releasing peptide receptors (GRPR) targeted positron emission tomography (PET) is a highly promising approach for imaging of prostate cancer (PCa) in small animal models and patients. Developing a GRPR-targeted PET probe with excellent in vivo performance such as high tumor uptake, high contrast and optimal pharmacokinetics is still very challenging. Herein, a novel bombesin (BBN) analog (named as SCH1) based on JMV594 peptide modified with an 8-amino octanoic acid spacer (AOC) was thus designed and conjugated with the metal chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA). The resulting NODAGA-SCH1 was then radiolabeled with 68Ga and evaluated for PET imaging of PCa. Compared with 68Ga-NODAGA-JMV594 probe, 68Ga-NODAGA-SCH1 exhibited excellent PET/CT imaging properties on PC-3 tumor-bearing nude mice, such as high tumor uptake (5.80 ± 0.42 vs 3.78 ± 0.28 %ID/g, 2h) and high tumor/muscle contrast (16.6 ± 1.50 vs 8.42 ± 0.61 %ID/g, 2h). Importantly, biodistribution data indicated a relatively similar accumulation of 68Ga-NODAGA-SCH1 was observed in the liver (4.21 ± 0.42 %ID/g) and kidney (3.41 ± 0.46 %ID/g) suggesting that the clearance is both through the kidney and the liver. Overall, 68Ga-NODAGA-SCH1 showed promising in vivo properties and is a promising candidate for translation into clinical PET-imaging of PCa patients.

Bioconjugate chemistry. 2016 Jul 11 [Epub ahead of print]

Yao Sun, Xiaowei Ma, Zhe Zhang, Ziyan Sun, Mathias Loft, Bingbing Ding, Changhao Liu, Liying Xu, Meng Yang, Yuxin Jiang, Jianfeng Liu, Yuling Xiao, Zhen Cheng, Xuechuan Hong