Tumor detection using ¹⁸F-labeled matrix metalloproteinase-2 inhibitor

Matrix metalloproteinase-2 (MMP-2) is a key enzyme involved in tumor invasiveness. (2R)-2- [4-(6-[¹⁸F]Fluorohex-1-ynyl)-benzenesulfonylamino]-3-methylbutyric acid ([¹⁸F]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 IC₅₀ value of 1.9 μM. Biodistribution study of [¹⁸F]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 [¹⁸F]SAV03M, a methyl ester of [¹⁸F]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 [¹⁸F]SAV03. Radio-thin-layer chromatographic analysis of [¹⁸F]SAV03M metabolites revealed that administered [¹⁸F]SAV03M was easily converted to the parent drug in vivo and accumulated in tumor tissue. Thus, [¹⁸F]SAV03M is suitable as the prodrug of [¹⁸F]SAV03 with potent efficacy. Whole body autoradiography using [¹⁸F]SAV03M also indicated tumor-specific accumulation of radioactivity, while higher accumulations in bone and intestinal contents were observed. Our results suggest that [¹⁸F]SAV03M could be potentially suitable for tumor imaging with PET.