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

• DOI: 10.1016/j.nucmedbio.2011.02.001
• Publication Date: 2011-04-22T19:18:44Z
• Authors: Yasuhiro Ohshima; Hirofumi Hanaoka; Shigeki Watanabe; Yumi Sugo; Satoshi Watanabe; Hideyuki Tominaga; Noboru Oriuchi; Keigo Endo; Noriko S. Ishioka
• Keywords: Male; Biological Transport; Adenocarcinoma; Mice; 03 medical and health sciences; 0302 clinical medicine; Drug Stability; Cell Line, Tumor; Drug Design; Positron-Emission Tomography; Colonic Neoplasms; Animals; Humans; Tyrosine

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.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.[(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.[(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.