Evaluation of radiofluorinated carboximidamides as potential IDO-targeted PET tracers for cancer imaging.
Evaluation of radiofluorinated carboximidamides as potential IDO-targeted PET tracers for cancer imaging.
复制标题
评估放射性氟羧酰胺作为癌症成像的潜在易于染料的宠物示踪剂。
DOI：
10.18632/oncotarget.14898
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发表时间：
2017-07-18
期刊：
影响因子：
--
通讯作者：
Tian H
中科院分区：
文献类型：
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作者：
Huang X;Pan Z;Doligalski ML;Xiao X;Ruiz E;Budzevich MM;Tian H
IDO1是一种沿着犬尿氨酸途径催化色氨酸分解代谢的起始和限速步骤的酶。IDO1的表达可通过局部阻断T淋巴细胞的增殖抑制免疫应答，提示IDO在免疫应答调节中起一定作用。这项研究的目的是评估放射性氟化羧胺作为IDO1的选择性PET放射性配基的潜力。通过体外、microPET实验测量，特异性结合与IDO1的表达相关。在表达IDO1的肿瘤中观察到新的放射性示踪剂[18F]IDO49的特异性积聚，并通过Western印迹和IHC分析证实。这些结果表明，[18F]IDO49有很大的潜力作为靶向肿瘤中IDO1的显像剂，因此可以作为IDO1靶向治疗的辅助诊断。
IDO1 is an enzyme catalyzing the initial and rate-limiting step in the catabolism of tryptophan along the kynurenine pathway. IDO1 expression could suppress immune responses by blocking T-lymphocyte proliferation locally, suggesting a role of IDO in the regulation of immune responses. The goal of this study was to evaluate the potential of radiofluorinated carboximidamides as selective PET radioligands for IDO1. Specific binding correlated with IDO1 expression as measured through in vitro, microPET experiments. Specific accumulation of the new radiotracer [18F]IDO49 was observed in IDO1-expressing tumors and confirmed by Western blot and IHC analyses. These results suggest that [18F]IDO49 has substantial potential as an imaging agent that targets IDO1 in tumors, and therefore may be utilized as a companion diagnostic for IDO1 targeted therapies.