Synthesis and Biological Evaluation of (S)-Amino-2-methyl-4-[⁷⁶Br]bromo-3-(E)-butenoic Acid (BrVAIB) for Brain Tumor Imaging

The novel compound, (S)-amino-2-methyl-4-[⁷⁶Br]bromo-3-(E)-butenoic acid (BrVAIB, [⁷⁶Br]5), was characterized against the known system A tracer, IVAIB ([¹²³I]8). [⁷⁶Br]5 was prepared in a 51% ± 19% radiochemical yield with high radiochemical purity (≥98%). The biological properties of [⁷⁶Br]5 were compared with those of [¹²³I]8. Results showed that [⁷⁶Br]5 undergoes mixed amino acid transport by system A and system L transport, while [¹²³I]8 had less uptake by system L. [⁷⁶Br]5 demonstrated higher uptake than [¹²³I]8 in DBT tumors 1 h after injection (3.7 ± 0.4% ID/g vs 1.5 ± 0.3% ID/g) and also showed higher uptake vs [¹²³I]8 in normal brain. Small animal PET studies with [⁷⁶Br]5 demonstrated good tumor visualization of intracranial DBTs up to 24 h with clearance from normal tissues. These results indicate that [⁷⁶Br]5 is a promising PET tracer for brain tumor imaging and lead compound for a mixed system A and system L transport substrate.