Synthesis and characterization of radioiodinated 3-phenethyl-2-indolinone derivatives for SPECT imaging of survivin in tumors.
Synthesis and characterization of radioiodinated 3-phenethyl-2-indolinone derivatives for SPECT imaging of survivin in tumors.
复制标题
用于肿瘤中生存素 SPECT 成像的放射性碘化 3-苯乙基-2-二氢吲哚酮衍生物的合成和表征。
DOI：
10.1016/j.bmc.2018.04.034
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
M. Nakayama,
中科院分区：
文献类型：
--
作者：
N. Ishikawa;T. Fuchigami;T. Mizoguchi;S. Yoshida;M. Haratake;M. Nakayama,
Survivin在大多数癌症中过度表达，与预后不良和对放疗和化疗的耐药性有关。本文报道了三种3-苯乙基-2-吲哚啉酮衍生物的合成及其在生存素体内显像剂中的应用。其中，3 -（2-（苯并[d][1,3]二氧二醇-5-基）-2-氧乙基）-3-羟基-5-碘吲哚林-2-one （IPI-1）对重组人survivin的结合亲和力最高（Kd= 68.3 nM）。体外研究表明，survivin阳性的MDA-MB-231细胞中的[125I]IPI-1结合明显高于survivin阴性的MCF-10A细胞。此外，MDA-MB-231细胞对[125I]IPI-1的摄取在高亲和力生存素配体S12的存在下呈剂量依赖性下降；这表明[125I]IPI-1在体外特异性结合细胞存活蛋白。MDA-MB-231荷瘤小鼠的生物分布研究表明，[125I]IPI-1在30 min时在肿瘤组织中摄取适度（1.37% ID/g），在180 min时降至0.32% ID/g。共注射S12（2.5 mg/kg）可略微降低肿瘤摄取和[125I]IPI-1的肿瘤/肌比值。虽然需要进一步的结构修饰来改善药代动力学特性，但我们的研究结果表明PI衍生物可能作为靶向survivin的肿瘤成像探针有用。
Survivin, overexpressed in most cancers, is associated with poor prognosis and resistance to radiation therapy and chemotherapy. Herein, we report the synthesis of three 3-phenethyl-2-indolinone derivatives and their application asin vivoimaging agents for survivin. Of these, 3-(2-(benzo[d][1,3]dioxol-5-yl)-2-oxoethyl)-3-hydroxy-5- iodoindolin-2-one (IPI-1) showed the highest binding affinity (Kd= 68.3 nM) to recombinant human survivin, as determined by quartz crystal microbalance (QCM).In vitrostudies demonstrated that the [125I]IPI-1 binding in survivin-positive MDA-MB-231 cells was significantly higher than that in survivin-negative MCF-10A cells. In addition, uptake of [125I]IPI-1 by MDA-MB-231 cells decreased in a dose-dependent manner in the presence of the high-affinity survivin ligand S12; this is indicative of specific binding of [125I]IPI-1 to cellular survivin proteinin vitro. Biodistribution studies in MDA-MB-231 tumor-bearing mice demonstrated the moderate uptake of [125I]IPI-1 in the tumor tissue (1.37% ID/g) at 30 min that decreased to 0.32% ID/g at 180 min. Co-injection of S12 (2.5 mg/kg) slightly reduced tumor uptake and the tumor/muscle ratio of [125I]IPI-1. Although further structural modifications are necessary to improve pharmacokinetic properties, our results indicate that PI derivatives may be useful as tumor-imaging probes targeting survivin.
培养物中 99mTc 标记寡核苷酸的非特异性细胞积累受其鸟嘌呤含量的影响。
影响因子：
3.1
作者：
Wang,Yi;Liu,Xinrong;Zhang,Yumin;Liu,Guozheng;Rusckowski,Mary;Hnatowich,DonaldJ
通讯作者：
Hnatowich,DonaldJ