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