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
StatePublished - Jan 28 2010

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Epithelial-Mesenchymal Transition
Positron-Emission Tomography
Heterografts
Sulfonic Acids
Lung Neoplasms
Neoplasms
Staining and Labeling
Cell Line

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Wu, Chunying ; Tang, Zhe ; Fan, Weiwen ; Zhu, Wenxia ; Wang, Changning ; Somoza, Edurado ; Owino, Norbert ; Li, Ruoshi ; Ma, Patrick Chi-Chung ; Wang, Yanming. / In vivo Positron Emission Tomography (PET) imaging of Mesenchymal - Epithelial Transition (MET) receptor. In: Journal of Medicinal Chemistry. 2010 ; Vol. 53, No. 1. pp. 139-146.
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Wu, C, Tang, Z, Fan, W, Zhu, W, Wang, C, Somoza, E, Owino, N, Li, R, Ma, PC-C & Wang, Y 2010, 'In vivo Positron Emission Tomography (PET) imaging of Mesenchymal - Epithelial Transition (MET) receptor', Journal of Medicinal Chemistry, vol. 53, no. 1, pp. 139-146. https://doi.org/10.1021/jm900803q

In vivo Positron Emission Tomography (PET) imaging of Mesenchymal - Epithelial Transition (MET) receptor. / Wu, Chunying; Tang, Zhe; Fan, Weiwen; Zhu, Wenxia; Wang, Changning; Somoza, Edurado; Owino, Norbert; Li, Ruoshi; Ma, Patrick Chi-Chung; Wang, Yanming.

In: Journal of Medicinal Chemistry, Vol. 53, No. 1, 28.01.2010, p. 139-146.

Research output: Contribution to journalArticle

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AU - Wu, Chunying

AU - Tang, Zhe

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AU - Wang, Changning

AU - Somoza, Edurado

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AU - Li, Ruoshi

AU - Ma, Patrick Chi-Chung

AU - Wang, Yanming

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