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

详细信息    查看全文

• 作者：Jennifer L. Burkemper ; Chaofeng Huang ; Aixiao Li ; Liya Yuan ; Keith Rich ; Jonathan McConathy ; Suzanne E. Lapi
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：November 12, 2015
• 年：2015
• 卷：58
• 期：21
• 页码：8542-8552
• 全文大小：468K
• ISSN：1520-4804

文摘

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% 卤 19% radiochemical yield with high radiochemical purity (鈮?8%). 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 卤 0.4%聽ID/g vs 1.5 卤 0.3%聽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.