Synthesis and preliminary biological evaluation of MMP inhibitor radiotracers [11C]methyl-halo-CGS 27023A analogs, new potential PET breast cancer imaging agents

Nucl Med Biol. 2002 Oct;29(7):761-70. doi: 10.1016/s0969-8051(02)00338-4.

Abstract

A series of [11C]methyl-halo-CGS 27023A analogs (2-F, 1a; 4-F, 1b; 2-Cl, 1c; 3-Cl, 1d; 4-Cl, 1e; 2-Br, 1f; 3-Br, 1g; 4-Br, 1h; 4-I, 1i), novel radiolabeled matrix metalloproteinase (MMP) inhibitors, have been synthesized for evaluation as new potential positron emission tomography (PET) breast cancer imaging agents. The precursors halo-CGS 27023A analogs (2-F, 6a; 4-F, 6b; 2-Cl, 6c; 3-Cl, 6d; 4-Cl, 6e; 2-Br, 6f; 3-Br, 6g; 4-Br, 6h; 4-I, 6i) for radiolabeling were obtained in four steps from starting material amino acid D-valine with moderate to excellent chemical yields. Precursors were labeled by [11C]methyl triflate through 11C-O-methylation method at the aminohydroxyl position under basic conditions and isolated by solid-phase extraction (SPE) purification to produce pure target compounds in 40-60% radiochemical yields (decay corrected to end of bombardment), in 20-25 min synthesis time.

Publication types

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

MeSH terms

  • Animals
  • Biomarkers, Tumor
  • Breast Neoplasms / diagnostic imaging
  • Carbon Radioisotopes / pharmacokinetics*
  • Humans
  • Hydroxamic Acids*
  • Metalloendopeptidases / antagonists & inhibitors
  • Metalloendopeptidases / metabolism*
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / pharmacokinetics*
  • Pyrazines*
  • Radiopharmaceuticals / pharmacokinetics
  • Sulfonamides
  • Tomography, Emission-Computed / methods*

Substances

  • Biomarkers, Tumor
  • CGS 27023A
  • Carbon Radioisotopes
  • Hydroxamic Acids
  • Protease Inhibitors
  • Pyrazines
  • Radiopharmaceuticals
  • Sulfonamides
  • Metalloendopeptidases