title: Design and synthesis of carbon-11-labeled dual aromatase-steroid sulfatase inhibitors as new potential PET agents for imaging of aromatase and steroid sulfatase expression in breast cancer.
abstract: Aromatase and steroid sulfatase (STS) are particularly attractive targets in the treatment of estrogen-receptor-positive breast cancer and the development of enzyme-based cancer imaging agents for the biomedical imaging technique positron emission tomography (PET). New carbon-11-labeled sulfamate derivatives were first designed and synthesized as potential PET dual aromatase-steroid sulfatase inhibitor (DASSI) radiotracers for imaging of aromatase and STS expression in breast cancer. The target tracers 5-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)-2-[(11)C]methoxyphenyl sulfamate ([(11)C]8a) and 4-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)-2-[(11)C]methoxyphenyl sulfamate ([(11)C]8b) were prepared from their corresponding precursors 5-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)-2-hydroxyphenyl sulfamate (16) and 4-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)-2-hydroxyphenyl sulfamate (21) with [(11)C]CH(3)OTf under basic conditions through the O-[(11)C]methylation and isolated by the reversed-phase high pressure liquid chromatography (HPLC) method in 30-45% radiochemical yields based on [(11)C]CO(2) and decay corrected to end of bombardment (EOB). The specific activity at end of synthesis (EOS) was 111-185GBq/micromol.
authors: Department of Radiology, Indiana University School of Medicine, 1345 West 16th Street, L3-208, Indianapolis, IN 46202, USA.
authors: Min
authors: M
authors: Wang
authors: Jarrett
authors: J
authors: Mickens
authors: Mingzhang
authors: M
authors: Gao
authors: Kathy D
authors: KD
authors: Miller
authors: George W
authors: GW
authors: Sledge
authors: Gary D
authors: GD
authors: Hutchins
authors: Qi-Huang
authors: QH
authors: Zheng
mesh_terms: D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics*; D002250:Carbon Radioisotopes; D015195:Drug Design; D015972:Gene Expression Regulation, Neoplastic; D007553:Isotope Labeling; D049268:Positron-Emission Tomography; D011854:Radiochemistry; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors*; D013451:Sulfonic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
chemical_list: D047072:Aromatase Inhibitors; D002250:Carbon Radioisotopes; D013451:Sulfonic Acids; C005741:sulfamic acid; D001141:Aromatase; D043266:Steryl-Sulfatase