Development of a widely usable amino acid tracer: ⁷⁶Br-α-methyl-phenylalanine for tumor PET imaging

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.