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 language||English (US)|
|Number of pages||8|
|Journal||Journal of Medicinal Chemistry|
|State||Published - 2010|
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Drug Discovery