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

Abstract

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 [18F]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 (18F) is the optimal PET radioisotope, and the creation of a [18F]AlF-peptide complex is a simple procedure.

METHODS:

C6 was conjugated to the bifunctional chelator NOTA (1, 4, 7-triazacyclononanetriacetic acid) for radiolabeling [18F]AlF conjugation. The MMP2-binding characteristics and tumor-targeting efficacy of [18F]AlF-NOTA-C6 were tested in vitro and in vivo.

RESULTS:

The non-decay corrected yield of [18F]AlF-NOTA-C6 was 46.2-64.2%, and the radiochemical purity exceeded 95%. [18F]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 [18F]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:

[18F]AlF-NOTA-C6 was easy to synthesize and has substantial potential as an imaging agent that targets MMP2 in tumors.

• Authors: Qinghua Liu, Donghui Pan, Chao Cheng, Dazhi Zhang, Anyu Zhang, Lizhen Wang, Hongdie Jiang, Tao Wang, Hongrui Liu, Yuping Xu, Runlin Yang, Fei Chen, Min Yang, Changjing Zuo
• Journal: PloS one (PLoS One) Vol. 10 Issue 11 Pg. e0141668 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26540114 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fluorine Radioisotopes
• Heterocyclic Compounds
• Heterocyclic Compounds, 1-Ring
• Ligands
• Peptides
• 1,4,7-triazacyclononane-N,N',N''-triacetic acid
• Matrix Metalloproteinase 2

Topics

• Cell Line, Tumor
• Fluorine Radioisotopes (administration & dosage)
• Heterocyclic Compounds (administration & dosage)
• Heterocyclic Compounds, 1-Ring
• Humans
• Ligands
• Matrix Metalloproteinase 2 (metabolism)
• Peptides (administration & dosage)
• Positron-Emission Tomography (methods)
• Radiochemistry (methods)
• Tissue Distribution