Development of tyrosine-based radiotracer 99mTc-N4-tyrosine for breast cancer imaging

Abstract

The purpose of this study was to develop an efficient way to synthesize 99mTc-O-[3-(1,4,8,11-tetraazabicyclohexadecane)-propyl]-tyrosine ( 99mTc-N4-Tyrosine), a novel amino acid-based radiotracer, and evaluate its potential in breast cancer gamma imaging. Precursor N4-Tyrosine was synthesized using a 5-step procedure, and its total synthesis yield was 38. It was successfully labeled with 99mTc with high radiochemical purity (95). Cellular uptake of 99mTc-N4-Tyrosine was much higher than that of 99mTc-N4 and the clinical gold standard 18F-2-deoxy-2- fluoro-glucose ( 18F-FDG) in rat breast tumor cells in vitro. Tissue uptake and dosimetry estimation in normal rats revealed that 99mTc-N4-Tyrosine could be safely administered to humans. Evaluation in breast tumor-bearing rats showed that although 99mTc-N4-Tyrosine appeared to be inferior to 188F-FDG in distinguishing breast tumor tissue from chemical-induced inflammatory tissue, it had high tumor-to-muscle uptake ratios and could detect breast tumors clearly by planar scintigraphic imaging. 99mTc-N4-Tyrosine could thus be a useful radiotracer for use in breast tumor diagnostic imaging. Copyright © 2012 Fan-Lin Kong et al.