Development of a Novel PET Tracer [18F]AlF-NOTA-C6 Targeting MMP2 for Tumor Imaging

作者：Liu, Qinghua^*; Pan, Donghui; Cheng, Chao; Zhang, Dazhi; Zhang, Anyu; Wang, Lizhen; Jiang, Hongdie; Wang, Tao; Liu, Hongrui; Xu, Yuping; Yang, Runlin; Chen, Fei; Yang, Min; Zuo, Changjing

来源：PLos One, 2015, 10(11): e0141668.

DOI：10.1371/journal.pone.0141668

• MATRIX-METALLOPROTEINASE EXPRESSION
• PROSTATE-CANCER
• GELATINASE ACTIVITY
• INHIBITOR
• MATRIX-METALLOPROTEINASE-2
• PROGRESSION
• PROGNOSIS
• PEPTIDE
• DESIGN
• CELLS

Background and Objective @@@ The overexpression of gelatinases, that is, matrix metalloproteinase MMP2 and MMP9, has been associated with tumor progression, invasion, and metastasis. To image MMP2 in tumors, we developed a novel ligand termed [F-18] AlF-NOTA-C6, with consideration that: c (KAHWGFTLD)NH2 (herein, C6) is a selective gelatinase inhibitor; Cy5.5-C6 has been visualized in many in vivo tumor models; positron emission tomography (PET) has a higher detection sensitivity and a wider field of view than optical imaging; fluorine-18 (F-18) is the optimal PET radioisotope, and the creation of a [F-18] AlF-peptide complex is a simple procedure. @@@ Methods @@@ C6 was conjugated to the bifunctional chelator NOTA (1, 4, 7-triazacyclononanetriacetic acid) for radiolabeling [F-18] AlF conjugation. The MMP2-binding characteristics and tumor-targeting efficacy of [F-18] AlF-NOTA-C6 were tested in vitro and in vivo. @@@ Results @@@ The non-decay corrected yield of [F-18] AlF-NOTA-C6 was 46.2-64.2%, and the radiochemical purity exceeded 95%. [F-18] AlF-NOTA-C6 was favorably retained in SKOV3 and PC3 cells, determined by cell uptake. Using NOTA-C6 as a competitive ligand, the uptake of [F-18] AlF-NOTA-C6 in SKOV3 cells decreased in a dose-dependent manner. In biodistribution and PET imaging studies, higher radioactivity concentrations were observed in tumors. Pre-injection of C6 caused a marked reduction in tumor tissue uptake. Immunohistochemistry showed MMP2 in tumor tissues. @@@ Conclusions @@@ [F-18]AlF-NOTA-C6 was easy to synthesize and has substantial potential as an imaging agent that targets MMP2 in tumors.

• 出版日期2015-11-5
• 单位复旦大学; 江苏省原子医学研究所; 中国人民解放军第二军医大学