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

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 [(18)F]AlF-NOTA-C6, with consideration that: c(KAHWGFTLD)NH(2) (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 ((18)F) is the optimal PET radioisotope, and the creation of a [(18)F]AlF-peptide complex is a simple procedure. METHODS: C6 was conjugated to the bifunctional chelator NOTA (1, 4, 7-triazacyclononanetriacetic acid) for radiolabeling [(18)F]AlF conjugation. The MMP2-binding characteristics and tumor-targeting efficacy of [(18)F]AlF-NOTA-C6 were tested in vitro and in vivo. RESULTS: The non-decay corrected yield of [(18)F]AlF-NOTA-C6 was 46.2–64.2%, and the radiochemical purity exceeded 95%. [(18)F]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 [(18)F]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: [(18)F]AlF-NOTA-C6 was easy to synthesize and has substantial potential as an imaging agent that targets MMP2 in tumors.