Synthesis and Biological Evaluation of (S)-Amino-2-methyl-4-[(76)Br]bromo-3-(E)-butenoic Acid (BrVAIB) for Brain Tumor Imaging.
Synthesis and Biological Evaluation of (S)-Amino-2-methyl-4-[(76)Br]bromo-3-(E)-butenoic Acid (BrVAIB) for Brain Tumor Imaging.
复制标题
DOI：
10.1021/acs.jmedchem.5b01035
复制
发表时间：
2015-11-12
影响因子：
7.3
通讯作者：
Lapi SE
中科院分区：
文献类型：
--
作者：
Bartels JL;Huang C;Li A;Yuan L;Rich K;McConathy J;Lapi SE
新化合物 (S)-氨基-2-甲基-4-[76Br]-溴-3-(E)-丁烯酸 (BrVAIB, [76Br]5) 通过已知的系统 A 示踪剂 IVAIB ([123I]8) 进行表征。 [76Br]5 的放射化学产率为 51% ± 19%，放射化学纯度高（≥98%）。将[76Br]5 的生物学特性与[123I]8 的生物学特性进行了比较。结果显示，[76Br]5 通过系统 A 和系统 L 进行混合氨基酸转运，而 [123I]8 被系统 L 摄取较少。注射后 1 小时，[76Br]5 在 DBT 肿瘤中表现出比 [123I]8 更高的摄取（3.7 ± 0.4% ID/g vs 1.5 ± 0.3% ID/g），并且在正常脑中也表现出比 [123I]8 更高的摄取。 [76Br]5 的小动物 PET 研究表明，颅内 DBT 的肿瘤可视化效果长达 24 小时，并能从正常组织中清除。这些结果表明，[76Br]5 是一种有前景的脑肿瘤成像 PET 示踪剂，也是混合系统 A 和系统 L 传输底物的先导化合物。
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.