title: Synthesis and preliminary biological evaluation of MMP inhibitor radiotracers [11C]methyl-halo-CGS 27023A analogs, new potential PET breast cancer imaging agents.
abstract: A series of [11C]methyl-halo-CGS 27023A analogs (2-F, 1a; 4-F, 1b; 2-Cl, 1c; 3-Cl, 1d; 4-Cl, 1e; 2-Br, 1f; 3-Br, 1g; 4-Br, 1h; 4-I, 1i), novel radiolabeled matrix metalloproteinase (MMP) inhibitors, have been synthesized for evaluation as new potential positron emission tomography (PET) breast cancer imaging agents. The precursors halo-CGS 27023A analogs (2-F, 6a; 4-F, 6b; 2-Cl, 6c; 3-Cl, 6d; 4-Cl, 6e; 2-Br, 6f; 3-Br, 6g; 4-Br, 6h; 4-I, 6i) for radiolabeling were obtained in four steps from starting material amino acid D-valine with moderate to excellent chemical yields. Precursors were labeled by [11C]methyl triflate through 11C-O-methylation method at the aminohydroxyl position under basic conditions and isolated by solid-phase extraction (SPE) purification to produce pure target compounds in 40-60% radiochemical yields (decay corrected to end of bombardment), in 20-25 min synthesis time.
authors.affiliation: Department of Radiology, Indiana University School of Medicine, 975 West Walnut Street, Room 028C, Indianapolis, IN 46202-5121, USA. qzheng@iupui.edu
authors.forename: Qi-Huang
authors.initials: QH
authors.lastname: Zheng
authors.forename: Xiangshu
authors.initials: X
authors.lastname: Fei
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.forename: Ji-Quan
authors.initials: JQ
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Bin Sun
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Mock
authors.forename: K
authors.initials: K
authors.lastname: Lee Stone
authors.forename: Tanya D
authors.initials: TD
authors.lastname: Martinez
authors.forename: Kathy D
authors.initials: KD
authors.lastname: Miller
authors.forename: George W
authors.initials: GW
authors.lastname: Sledge
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hutchins
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000000981:diagnostic imaging; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics*; D006801:Humans; D006877:Hydroxamic Acids; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011719:Pyrazines; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013449:Sulfonamides; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; C097658:CGS 27023A; D002250:Carbon Radioisotopes; D006877:Hydroxamic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D019275:Radiopharmaceuticals; D013449:Sulfonamides; D008666:Metalloendopeptidases