Development of 76Br-labeled {alpha}-methyl L-phenylalanine for imaging tumors

1051 Objectives Br-76 (76Br) is an attractive positron emitter due to its long half-life (t1/2=16.1 h). In this study, 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) were designed, and their potential as a tumor imaging agent was evaluated. Methods 77Br, radiobromine with longer half-life, labeled amino acid derivatives were used for basic studies. The stannyl precursor of each BAMP was radiobrominated using N-chlorosuccinimide as an oxidant. Plasma stability and plasma protein binding were evaluated with freshly prepared murine plasma. Biodistribution in normal mice and cellular uptake studies using LS180 cell line were performed. Results Both [77Br]-BAMP remained intact over 6 h after incubation in the plasma. Plasma protein binding of 4-[77Br]-BAMP was higher than that of 2-[77Br]-BAMP. In biodistribution studies, 4-[77Br]-BAMP showed slower blood clearance and higher renal accumulation (2.96 ± 0.17 and 22.0 ± 2.67 % ID/g at 1 h after injection, respectively) than did 2-[77Br]-BAMP (0.55 ± 0.19 and 3.15 ± 0.98 % ID/g at 1 h after injection, respectively). More than 90% of injected radioactivity was excreted in the urine by 6 h post-injection of 2-[77Br]-BAMP. While both [77Br]-BAMP were taken up by LS180 cell and inhibited by a L-type amino acid transporter1 inhibitor, 2-[77Br]-BAMP exhibited higher uptake than 4-[77Br]-BAMP. Conclusions 2-[77Br]-BAMP exhibited preferred pharmacokinetics, partially due to lower plasma protein binding, and higher LS180 cell uptake than 4-[77Br]-BAMP. These findings suggest that 2-[76Br]-BAMP would constitute a potential new PET tracer for tumor imaging.