In vivo positron emission tomography (PET) imaging of mesenchymal-epithelial transition (MET) receptor

J Med Chem. 2010 Jan 14;53(1):139-46. doi: 10.1021/jm900803q.

Abstract

We report the radiosynthesis and evaluation of 3-[3,5-dimethyl-4-(4-[11C]methylpiperazinecarbonyl)-1H-pyrrol-2-ylmethylene]-2-oxo-2,3-dihydro-1H-indole-5-sulfonic acid (3-chlorophenyl)methylamide, termed [11C]SU11274 ([11C]14) for in vivo imaging of mesenchymal-epithelial transition (MET) receptor by positron emission tomography (PET). Following the synthesis of the precursor (13) that was achieved in 10 steps with a total yield of 9.7%, [11C]14 was obtained through radiomethylation in a range of 5-10% radiochemical yield and over 95% radiochemical purity. For in vivo PET studies, two human lung cancer xenograft models were established using MET-positive NCI-H1975 and MET-negative NCI-H520 cell lines. Quantitative [11C]14-PET studies showed that the tumor uptake of [11C]14 in the NCI-H1975 xenografts was significantly higher than that in the NCI-H520 xenografts, which is consistent with their corresponding immunohistochemical tissue staining patterns of MET receptors from the same animals. These studies demonstrated that [11C]14-PET is an appropriate imaging marker for quantification of MET receptor in vivo, which can facilitate efficacy evaluation in the clinical development of MET-targeted cancer therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Cell Line, Tumor
  • Drug Evaluation
  • ErbB Receptors / metabolism
  • Humans
  • Indoles* / chemical synthesis
  • Indoles* / chemistry
  • Lung Neoplasms / diagnostic imaging*
  • Lung Neoplasms / drug therapy
  • Mice
  • Mice, Nude
  • Molecular Imaging*
  • Piperazines* / chemical synthesis
  • Piperazines* / chemistry
  • Positron-Emission Tomography*
  • Receptor Protein-Tyrosine Kinases / chemistry*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Sulfonamides* / chemical synthesis
  • Sulfonamides* / chemistry
  • Xenograft Model Antitumor Assays

Substances

  • ((3Z)-N-(3-chlorophenyl)-3-((3,5-dimethyl-4-((4-methylpiperazin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide)
  • Antineoplastic Agents
  • Indoles
  • Piperazines
  • Sulfonamides
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases