In vivo Positron Emission Tomography (PET) imaging of Mesenchymal - Epithelial Transition (MET) receptor

Chunying Wu, Zhe Tang, Weiwen Fan, Wenxia Zhu, Changning Wang, Edurado Somoza, Norbert Owino, Ruoshi Li, Patrick Chi-Chung Ma, Yanming Wang

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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.

Original languageEnglish (US)
Pages (from-to)139-146
Number of pages8
JournalJournal of Medicinal Chemistry
Volume53
Issue number1
DOIs
Publication statusPublished - Jan 28 2010

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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