Preparation and biological evaluation of 3-[76Br]bromo-α-methyl-l-tyrosine, a novel tyrosine analog for positron emission tomography imaging of tumors

Introduction 3-[ 18 F]fluoro-α-methyl-l-tyrosine ([ 18 F]FAMT) is a useful amino acid tracer for positron emission tomography (PET) imaging of malignant tumors. FAMT analogs labeled with 76 Br, a positron emitter with a long half-life ( t 1/2 =16.1 h), could potentially be widely used as amino acid tracers for tumor imaging. In this study, 3-[ 76 Br]bromo-α-methyl-l-tyrosine ([ 76 Br]BAMT) was designed, and its usefulness was evaluated as a novel PET tracer for imaging malignant tumors. Methods In this study, both [ 76 Br]BAMT and [ 77 Br]BAMT were prepared. The in vitro and in vivo stability of [ 77 Br]BAMT was evaluated by HPLC analysis. Cellular uptake and retention of [ 77 Br]BAMT and [ 18 F]FAMT were evaluated using LS180 colon adenocarcinoma cells. Biodistribution studies were performed in normal mice and in LS180 tumor-bearing mice, and the tumors were imaged with a small-animal PET scanner. Results [ 77 Br]BAMT was stable in vitro but was catabolized after administration in mice. Cellular accumulation and retention of [ 77 Br]BAMT were significantly higher than those of [ 18 F]FAMT. In biodistribution studies, the tumor accumulation of [ 77 Br]BAMT was higher than that of [ 18 F]FAMT. However, some level of debromination was seen, which caused more retention of radioactivity in the blood and organs than was seen with [ 18 F]FAMT. PET imaging with [ 76 Br]BAMT enabled clear visualization of the tumor, and the whole-body image using [ 76 Br]BAMT was similar to that using [ 18 F]FAMT. Conclusions [ 77 Br]BAMT showed high levels of tumor accumulation, and [ 76 Br]BAMT enabled clear visualization of the tumor by PET imaging. Although an improvement in stability is still needed, 76 Br-labeled FAMT analogs could potentially serve as PET tracers for the imaging of malignant tumors.