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 |
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Authors: | Min Wang Jarrett Mickens Mingzhang Gao Kathy D Miller George W Sledge Gary D Hutchins Qi-Huang Zheng |
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Institution: | aDepartment of Radiology, Indiana University School of Medicine, 1345 West 16th Street, L3-208, Indianapolis, IN 46202, USA;bDepartment of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA |
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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)-2-11C]methoxyphenyl sulfamate (11C]8a) and 4-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)-2-11C]methoxyphenyl sulfamate (11C]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 11C]CH3OTf under basic conditions through the O-11C]methylation and isolated by the reversed-phase high pressure liquid chromatography (HPLC) method in 30–45% radiochemical yields based on 11C]CO2 and decay corrected to end of bombardment (EOB). The specific activity at end of synthesis (EOS) was 111–185 GBq/μmol. |
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Keywords: | Positron emission tomography Aromatase Steroid sulfatase Sulfamate derivatives Radiotracers Cancer imaging |
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