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Tumor detection using 18F-labeled matrix metalloproteinase-2 inhibitor
Shozo Furumoto1, Kyoka Takashima, Kazuo Kubota
1Institute of Development, Aging and Cancer and Graduate School of Pharmaceutical Scinces, Tohoku University, Sendai, Japan. shozo@idac.tohoku.ac.jp
Abstract:
Matrix metalloproteinase-2 (MMP-2) is a key enzyme involved in tumor invasiveness. (2R)-2- [4-(6-[(18)F]Fluorohex-1-ynyl)-benzenesulfonylamino]-3-methylbutyric acid ([(18)F]SAV03), a new fluorine-18 labeled MMP-2 inhibitor developed for tumor imaging with PET, was biologically evaluated using in vivo tumor model. Enzymatic MMP-2 assay of SAV03 yielded an IC(50) value of 1.9 microM. Biodistribution study of [(18)F]SAV03 using Ehrlich tumor bearing mice showed that the uptake in tumor was higher than in other organs, except for the liver, small intestine, and bone. When [(18)F]SAV03M, a methyl ester of [(18)F]SAV03, was used as a prodrug, the uptake in liver at 30 min after injection decreased by half and that in tumor increased by 2.4 times, compared with [(18)F]SAV03. Radio-thin-layer chromatographic analysis of [(18)F]SAV03M metabolites revealed that administered [(18)F]SAV03M was easily converted to the parent drug in vivo and accumulated in tumor tissue. Thus, [(18)F]SAV03M is suitable as the prodrug of [(18)F]SAV03 with potent efficacy. Whole body autoradiography using [(18)F]SAV03M also indicated tumor-specific accumulation of radioactivity, while higher accumulations in bone and intestinal contents were observed. Our results suggest that [(18)F]SAV03M could be potentially suitable for tumor imaging with PET.
Insights
A novel fluorine-18 labeled inhibitor, [(18)F]SAV03M, shows potent efficacy as a prodrug for matrix metalloproteinase-2 (MMP-2) imaging. This compound demonstrates enhanced tumor accumulation, making it a promising candidate for positron emission tomography (PET) tumor imaging.
Area of Science:
- Radiopharmaceutical Chemistry
- Molecular Imaging
- Oncology
Background:
- Matrix metalloproteinase-2 (MMP-2) is crucial for tumor invasion.
- Developing targeted imaging agents for MMP-2 is vital for cancer diagnostics.
Purpose of the Study:
- To evaluate the biological efficacy of [(18)F]SAV03M, a novel fluorine-18 labeled MMP-2 inhibitor prodrug.
- To assess its potential for positron emission tomography (PET) tumor imaging.
Main Methods:
- In vivo evaluation using an Ehrlich tumor-bearing mouse model.
- Biodistribution studies and radio-thin-layer chromatography for metabolite analysis.
- Whole body autoradiography to determine tissue distribution.
Main Results:
- [(18)F]SAV03M demonstrated effective conversion to the parent drug in vivo.
- The prodrug [(18)F]SAV03M showed a 2.4-fold increase in tumor uptake compared to [(18)F]SAV03.
- Tumor-specific accumulation of radioactivity was observed with [(18)F]SAV03M.
Conclusions:
- [(18)F]SAV03M is a potent prodrug of [(18)F]SAV03 with enhanced tumor targeting capabilities.
- This agent shows significant potential for effective tumor imaging using PET.
