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

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• 作者：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
• 刊名：Bioconjugate Chemistry
• 出版年：2016
• 出版时间：August 17, 2016
• 年：2016
• 卷：27
• 期：8
• 页码：1857-1864
• 全文大小：430K
• 年卷期：0
• ISSN：1520-4812

文摘

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,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, 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 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 through both 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.