title: In vivo positron emission tomography (PET) imaging of mesenchymal-epithelial transition (MET) receptor.
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.
authors.affiliation: Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Chunying
authors.initials: C
authors.lastname: Wu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Tang
authors.forename: Weiwen
authors.initials: W
authors.lastname: Fan
authors.forename: Wenxia
authors.initials: W
authors.lastname: Zhu
authors.forename: Changning
authors.initials: C
authors.lastname: Wang
authors.forename: Edurado
authors.initials: E
authors.lastname: Somoza
authors.forename: Norbert
authors.initials: N
authors.lastname: Owino
authors.forename: Ruoshi
authors.initials: R
authors.lastname: Li
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Ma
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry; D045744:Cell Line, Tumor; D004341:Drug Evaluation; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry; D049268:Positron-Emission Tomography; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: C478479:((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); D000970:Antineoplastic Agents; D007211:Indoles; D010879:Piperazines; D013449:Sulfonamides; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases