Synthesis and Evaluation of Amino Acid-Based Radiotracer99mTc-N4-AMT for Breast Cancer Imaging

Abstract

Purpose. This study was to develop an efficient synthesis of99mTc-O-[3-(1,4,8,11-tetraazabicyclohexadecane)-propyl]-α-methyl tyrosine (99mTc-N4-AMT) and evaluate its potential in cancer imaging.Methods. N4-AMT was synthesized by reacting N4-oxalate and 3-bromopropyl AMT (N-BOC, ethyl ester).In vitrocellular uptake kinetics of99mTc-N4-AMT was assessed in rat mammary tumor cells. Tissue distribution of the radiotracer was determined in normal rats at 0.5–4 h, while planar imaging was performed in mammary tumor-bearing rats at 30–120 min.Results. The total synthesis yield of N4-AMT was 14%. Cellular uptake of99mTc-N4-AMT was significantly higher than that of99mTc-N4. Planar imaging revealed that99mTc-N4-AMT rendered greater tumor/muscle ratios than99mTc-N4.Conclusions. N4-AMT could be synthesized with a considerably high yield. Ourin vitroandin vivodata suggest that99mTc-N4-AMT, a novel amino acid-based radiotracer, efficiently enters breast cancer cells, effectively distinguishes mammary tumors from normal tissues, and thus holds the promise for breast cancer imaging.