Synthesis and in vitro cellular uptake of 11C-labeled 5-aminolevulinic acid derivative to estimate the induced cellular accumulation of protoporphyrin IX.
Synthesis and in vitro cellular uptake of 11C-labeled 5-aminolevulinic acid derivative to estimate the induced cellular accumulation of protoporphyrin IX.
复制标题
11C 标记的 5-氨基乙酰丙酸衍生物的合成和体外细胞摄取，以估计原卟啉 IX 诱导的细胞积累。
DOI：
10.1016/j.bmcl.2013.06.025
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发表时间：
2013
影响因子：
2.7
通讯作者：
Saga T.
中科院分区：
文献类型：
--
作者：
Suzuki C;Kato K;Tsuji AB;Kikuchi T;Zhang MR;Arano Y;Saga T.
由外源性5-氨基乙酰丙酸（ALA）诱导的原卟啉IX（PpIX）在肿瘤中的积累影响基于ALA的光动力和声动力疗法的治疗功效。为了开发一种新的成像探针来评估ALA诱导的PpIX积累，11 C标记的ALA类似物（4），一种ALA-乙酰化酶抑制剂，通过在四丁基氟化铵存在下对席夫碱活化的前体进行11 C-甲基化，然后水解酯和亚胺基团来放射合成。细胞对4的摄取随时间呈线性增加，并被ALA和其他转运蛋白竞争者抑制。用正电子发射断层扫描监测类似物4可能有助于估计ALA诱导的PpIX在肿瘤中的积聚。
Protoporphyrin IX (PpIX) accumulation induced by exogenous 5-aminolevulinic acid (ALA) in tumors affects the therapeutic efficacy of ALA-based photodynamic and sonodynamic therapies. To develop a new imaging probe to estimate the ALA-induced PpIX accumulation,11C-labeled ALA analog (4), an ALA-dehydratase inhibitor, was radiosynthesized via11C-methylation of a Schiff-base-activated precursor in the presence of tetrabutylammonium fluoride, followed by the hydrolysis of ester and imine groups. The cellular uptake of4linearly increased with time and was inhibited by ALA and other transporter competitors. Monitoring analog4with positron emission tomography might be useful to estimate the ALA-induced PpIX accumulation in tumors.