Synthesis of a New Carbon-11–Labeled Sulfamate Derivative as a Potential PET Tracer for Imaging of Breast Cancer Aromatase and Steroid Sulfatase Expression

Abstract

A carbon-11-labeled sulfamate derivative was designed and synthesized as a new potential positron-emission-tomography dual aromatase–steroid sulfatase inhibitor radiotracer for imaging of aromatase and steroid sulfatase expression in breast cancer. The target tracer 2-chloro-4-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)-6-[¹¹C]methoxyphenyl sulfamate ([¹¹C]7) was prepared from its corresponding precursor 2-chloro-4-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)-6-hydroxyphenyl sulfamate (18) with [¹¹C]CH₃OTf under basic conditions through the O-[¹¹C]methylation and isolated by the reversed-phase high-performance liquid chromatography in 40–45% radiochemical yields based on [¹¹C]CO₂ and decay corrected to end of bombardment. The specific activity at end of synthesis was 111-185 GBq/μmol.

Keywords:

• Aromatase
• cancer imaging
• positron emission tomography
• radiotracer
• steroid sulfatase
• sulfamate derivative

ACKNOWLEDGMENTS

This work was partially supported by the Susan G. Komen for the Cure, Breast Cancer Research Foundation, and Indiana Genomics Initiative (INGEN) of Indiana University, which is supported in part by Lilly Endowment Inc. The authors thank Dr. Bruce H. Mock and Barbara E. Glick-Wilson for their assistance in production of [¹¹C]CH₃OTf. ¹H NMR spectra were recorded on a Bruker Avance II 500-MHz NMR spectrometer in the Department of Chemistry and Chemical Biology at Indiana University Purdue University Indianapolis (IUPUI), which is supported by NSF-MRI Grant CHE-0619254. The referee's criticisms and editor's comments for the revision of the manuscript are greatly appreciated.