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

Gastrin-releasing peptide receptor (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) analogue (named 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,l-glutaric acid 4,7-acetic acid (NODAGA). The resulting NODAGA-SCH1 was then radiolabeled with Ga-68 and evaluated for PET imaging of PCa. Compared with Ga-68-NODAGA-JMV594 probe, Ga-68-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, 2 h) and high tumor/muscle contrast (16.6 +/- 1.50 vs 8.42 +/- 0.61%ID/g, 2 h). Importantly, biodistribution data indicated a relatively similar accumulation of Ga-68-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 through both the kidney and the liver. Overall, Ga-68-NODAGA-SCH1 showed promising in vivo properties and is a promising candidate for translation into clinical PET-imaging of PCa patients.