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

Abstract

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.

• Authors: Yasuhiro Ohshima, Hirofumi Hanaoka, Shigeki Watanabe, Yumi Sugo, Satoshi Watanabe, Hideyuki Tominaga, Noboru Oriuchi, Keigo Endo, Noriko S Ishioka
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 38 Issue 6 Pg. 857-65 (Aug 2011) ISSN: 1872-9614 [Electronic] United States
• PMID: 21843782 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• 3-bromo-alpha-methyltyrosine
• Tyrosine

Topics

• Adenocarcinoma (diagnostic imaging, metabolism, pathology)
• Animals
• Biological Transport
• Cell Line, Tumor
• Colonic Neoplasms (diagnostic imaging, metabolism, pathology)
• Drug Design
• Drug Stability
• Humans
• Male
• Mice
• Positron-Emission Tomography (methods)
• Tyrosine (analogs & derivatives, blood, metabolism, pharmacokinetics)