title: Synthesis of [11C]CX-6258 as a new PET tracer for imaging of Pim kinases in cancer.
abstract: The reference standard CX-6258 {(E)-5-chloro-3-((5-(3-(4-methyl-1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)indolin-2-one, 4a} and its desmethylated precursor N-desmethyl-CX-6258 {(E)-3-((5-(3-(1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)-5-chloroindolin-2-one, 5} for radiolabeling were synthesized from 5-bromo-2-furaldehyde and 3-carboxybenzeneboronic acid in 3 and 4 steps with 29-49% and 24-32% overall chemical yield, respectively. The target tracer [(11)C]CX-6258 {(E)-5-chloro-3-((5-(3-(4-[(11)C]methyl-1,4-diazepane-1-carbonyl)phenyl)furan-2-yl)methylene)indolin-2-one, [(11)C]4a} was prepared from N-desmethyl-CX-6258 (5) with [(11)C]CH3OTf under basic condition (2N NaOH) through N-[(11)C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 40-50% radiochemical yield based on [(11)C]CO2 and decay corrected to end of bombardment (EOB) with 370-1110GBq/μmol specific activity at EOB.
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
authors.forename: Reynaldo
authors.initials: R
authors.lastname: Tzintzun
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
authors.forename: Mingzhang
authors.initials: M
authors.lastname: Gao
authors.affiliation: Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, College of Chemistry and Environmental Science, Hebei University, Baoding, Hebei 071002, China.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA. Electronic address: qzheng@iupui.edu.
authors.forename: Qi-Huang
authors.initials: QH
authors.lastname: Zheng
mesh_terms: D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000201:enzymology; D049268:Positron-Emission Tomography; D051573:Proto-Oncogene Proteins c-pim-1 / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001381:Azepines; C000607921:CX-6258; D002250:Carbon Radioisotopes; D007211:Indoles; D019275:Radiopharmaceuticals; D051573:Proto-Oncogene Proteins c-pim-1; C406031:proto-oncogene proteins pim
keywords: Cancer; Pim kinases; Positron emission tomography (PET); Radiosynthesis; [(11)C]CX-6258