Synthesis and evaluation pf 11C-labeled coumarin analog as an imaging probe for detecting monocarboxylate transporters expression
Synthesis and evaluation pf 11C-labeled coumarin analog as an imaging probe for detecting monocarboxylate transporters expression
复制标题
作为检测单羧酸转运蛋白表达的成像探针的 11C 标记香豆素类似物的合成和评估
DOI：
10.1016/j.bmcl.2017.09.033
复制
发表时间：
2017
影响因子：
2.7
通讯作者：
Y.; Higashi. T.
中科院分区：
文献类型：
--
作者：
Tateishi;H.; Tsuji;A. B.; Kato;K.; Sudo;H.; Sugyo;A.; Hanakawa;T.; Zhang;M. R.; Saga;T.; Arano;Y.; Higashi. T.
肿瘤中上调的单羧酸转运蛋白（MCT）被认为是诊断成像靶点。在此，我们合成了正电子发射断层扫描探针候选香豆素类似物2和3，并显示2对MCT的亲和力比代表性MCT抑制剂高55倍。而[11 C] 2显示出低的肿瘤蓄积，可能是由于与血浆蛋白形成加合物，[11 C] 2显示出高的初始脑摄取，这表明2的支架具有在星形胶质细胞-神经元乳酸穿梭的成像探针中优选的性质。尽管还需要进一步优化2，我们的研究结果可用于开发MCT靶向显像剂。
Upregulated monocarboxylate transporters (MCTs) in tumors are considered diagnostic imaging targets. Herein, we synthesized the positron emission tomography probe candidates coumarin analogs2and3, and showed 55 times higher affinity of2for MCTs than a representative MCT inhibitor. Whereas[11C]2showed low tumor accumulation, probably due to adduct formation with plasma proteins,[11C]2showed high initial brain uptake, suggesting that the scaffold of2has properties that are preferable in imaging probes for the astrocyte–neuron lactate shuttle. Although further optimization of2is required, our findings can be used to inform the development of MCT-targeted imaging agents.