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

Nucl Med Biol. 2003 Feb;30(2):119-25. doi: 10.1016/s0969-8051(02)00393-1.


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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography / methods
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Ehrlich Tumor / diagnostic imaging*
  • Carcinoma, Ehrlich Tumor / metabolism*
  • Female
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase Inhibitors
  • Metabolic Clearance Rate
  • Mice
  • Mice, Inbred Strains
  • Neoplasm Transplantation
  • Organ Specificity
  • Radiopharmaceuticals / pharmacokinetics
  • Sulfonamides / pharmacokinetics*
  • Tissue Distribution
  • Tomography, Emission-Computed / methods
  • Valine / analogs & derivatives
  • Valine / pharmacokinetics*
  • Whole-Body Counting


  • 2-(4-(6-fluorohex-1-ynyl)benzenesulfonylamino)-3-methylbutyric acid
  • Biomarkers, Tumor
  • Matrix Metalloproteinase Inhibitors
  • Radiopharmaceuticals
  • Sulfonamides
  • Matrix Metalloproteinase 2
  • Valine