Development Of Tyrosine-Based Radiotracer Tc-99m-N4-Tyrosine For Breast Cancer Imaging

The purpose of this study was to develop an efficient way to synthesize Tc-99m-O-[3-(1,4,8,11-tetraazabicyclohexadecane)-propyl]tyrosine (Tc-99m-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 Tc-99m with high radiochemical purity (>95%). Cellular uptake of Tc-99m-N4-Tyrosine was much higher than that of Tc-99m-N4 and the clinical gold standard F-18-2-deoxy-2-fluoro-glucose (F-18-FDG) in rat breast tumor cells in vitro. Tissue uptake and dosimetry estimation in normal rats revealed that Tc-99m-N4-Tyrosine could be safely administered to humans. Evaluation in breast tumor-bearing rats showed that although Tc-99m-N4-Tyrosine appeared to be inferior to F-18-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. Tc-99m-N4-Tyrosine could thus be a useful radiotracer for use in breast tumor diagnostic imaging.