PT  - JOURNAL ARTICLE
AU  - Hirofumi Hanaoka
AU  - Yasuhiro Ohshima
AU  - Yurika Suzuki
AU  - Aiko Yamaguchi
AU  - Shigeki Watanabe
AU  - Tomoya Uehara
AU  - Shushi Nagamori
AU  - Yoshikatsu Kanai
AU  - Noriko S. Ishioka
AU  - Yoshito Tsushima
AU  - Keigo Endo
AU  - Yasushi Arano
TI  - Development of a Widely Usable Amino Acid Tracer: <sup>76</sup>Br-α-Methyl-Phenylalanine for Tumor PET Imaging
AID  - 10.2967/jnumed.114.152215
DP  - 2015 May 01
TA  - Journal of Nuclear Medicine
PG  - 791--797
VI  - 56
IP  - 5
4099  - http://jnm.snmjournals.org/content/56/5/791.short
4100  - http://jnm.snmjournals.org/content/56/5/791.full
SO  - J Nucl Med2015 May 01; 56
AB  - Radiolabeled amino acids are superior PET tracers for the imaging of malignant tumors, and amino acids labeled with 76Br, an attractive positron emitter because of its relatively long half-life (16.2 h), could potentially be a widely usable tumor imaging tracer. In this study, in consideration of its stability and tumor specificity, we designed two 76Br-labeled amino acid derivatives, 2-76Br-bromo-α-methyl-l-phenylalanine (2-76Br-BAMP) and 4-76Br-bromo-α-methyl-l-phenylalanine (4-76Br-BAMP), and investigated their potential as tumor imaging agents. Methods: Both 76Br- and 77Br-labeled amino acid derivatives were prepared. We performed in vitro and in vivo stability studies and cellular uptake studies using the LS180 colon adenocarcinoma cell line. Biodistribution studies in normal mice and in LS180 tumor–bearing mice were performed, and the tumors were imaged with a small-animal PET scanner. Results: Both 77Br-BAMPs were stable in the plasma and in the murine body. Although both 77Br-BAMPs were taken up by LS180 cells and the uptake was inhibited by L-type amino acid transporter 1 inhibitors, 2-77Br-BAMP exhibited higher uptake than 4-77Br-BAMP. In the biodistribution studies, 2-77Br-BAMP showed more rapid blood clearance and lower renal accumulation than 4-77Br-BAMP. More than 90% of the injected radioactivity was excreted in the urine by 6 h after the injection of 2-77Br-BAMP. High tumor accumulation of 2-77Br-BAMP was observed in tumor-bearing mice, and PET imaging with 2-76Br-BAMP enabled clear visualization of the tumors. Conclusion: 2-77Br-BAMP exhibited preferred pharmacokinetics and high LS180 tumor accumulation, and 2-76Br-BAMP enabled clear visualization of the tumors by PET imaging. These findings suggest that 2-76Br-BAMP could constitute a potential new PET tracer for tumor imaging and may eventually enable the wider use of amino acid tracers.