Indirectly radioiodinated exendin-4 as an analytical tool for in vivo detection of glucagon-like peptide-1 receptor in a disease setting
Indirectly radioiodinated exendin-4 as an analytical tool for in vivo detection of glucagon-like peptide-1 receptor in a disease setting
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间接放射性碘化 exendin-4 作为疾病环境中胰高血糖素样肽-1 受体体内检测的分析工具
DOI：
10.1007/s12149-020-01540-0
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发表时间：
2020
影响因子：
2.6
通讯作者：
Temma Takashi
中科院分区：
文献类型：
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作者：
Kondo Naoya;Oishi Ayaka;Hirata Masahiko;Temma Takashi
胰高血糖素样肽-1受体激动剂（GLP-1 RA）已被报道对糖尿病和多种疾病具有治疗作用。GLP-1受体（GLP-1 R）的精确检测可用于诊断和阐明此类疾病的机制。本研究旨在开发一种基于GLP-1 RA的成像探针，该探针具有高摩尔活性和灵敏度，可用于检测非胰腺疾病中低水平GLP-1 R表达。方法我们选择激动剂exenglutamine（Ex 4）作为GLP-1 R靶向探针的亲本肽，通过在N-末端添加Cys残基并用辅剂N-末端标记来制备Cys-Ex 4。（3-[125 I]碘苯基）马来酰亚胺我们评估了[125 I] Ex 4 ipm对GLP-1 R的亲和力，以及胰岛素瘤和前列腺癌细胞系中的细胞结合谱，以及正常和荷瘤小鼠的体内生物分布，以评估组织中GLP-1 R依赖性放射性蓄积。Ex 4 ipm通过硫醇/马来酰亚胺反应容易地合成，具有高放射化学产率（73%）、放射化学纯度（> 99%）和摩尔活性（81 GBq/μmol）。小鼠给药后，[125 I] Ex 4 ipm在胰腺中蓄积至高水平（23.3% ID/g），放射性共定位于胰岛素阳性β细胞区域。在过表达GLP-1 R的胰岛素瘤中也蓄积了大量放射性（27.5% ID/g）。相比之下，低量的[125 I] Ex 4 ipm积累，对应于低表达水平的GLP-1 R，在前列腺癌细胞和异种移植物中观察到作为非胰腺application.ConclusionOur结果表明，[123 I] Ex 4 ipm可能是有价值的GLP-1 R成像糖尿病，胰岛素瘤，和各种疾病相关的GLP-1 R。
ObjectiveGlucagon-like peptide-1 receptor agonist (GLP-1RA) has been reported to have therapeutic effects on diabetes and various diseases. Precise detection of GLP-1 receptor (GLP-1R) can be useful to diagnose and elucidate the mechanism of such diseases. Here we aimed to develop an imaging probe based on GLP-1RA that has high molar activity and sensitivity for detection of low-level GLP-1R expression in non-pancreatic diseases.MethodsWe selected the agonist exenatide (Ex4) as the parent peptide of a GLP-1R targeting probe and prepared Cys-Ex4 by addition of an N-terminal Cys residue and labeling with the prosthetic agentN-(3-[125I]iodophenyl)maleimide ([125I]IPM) to generate [125I]Ex4ipm.We evaluated the affinity of [125I]Ex4ipmfor GLP-1R, as well as cellular binding profiles in insulinoma and prostate cancer cell lines, and in vivo biodistributions in normal and tumor-bearing mice to assess GLP-1R-dependent accumulation of radioactivity in tissues.Results[125I]Ex4ipmwas easily synthesized with high radiochemical yield (73%), radiochemical purity (> 99%), and molar activity (81 GBq/µmol) via a thiol/maleimide reaction. Following administration to mice, [125I]Ex4ipmaccumulated to high levels in the pancreas (23.3% ID/g), with radioactivity co-localizing in areas having insulin-positive β cells. High amounts of radioactivity also accumulated in insulinomas that overexpressed GLP-1R (27.5% ID/g). In contrast, low amounts of [125I]Ex4ipmaccumulation, corresponding to low expression levels of GLP-1R, were observed in prostate cancer cells and xenografts used as a model of non-pancreatic applications.ConclusionOur results suggested that [123I]Ex4ipmcould be valuable for GLP-1R imaging in diabetes, insulinomas, and various diseases related to GLP-1R.
放射性固化的Exendin-4优于辐射标记的胰高血糖素样肽-1受体探针，探针克服了高肾脏的摄取。
影响因子：
3.7
作者：
Läppchen T;Tönnesmann R;Eersels J;Meyer PT;Maecke HR;Rylova SN
通讯作者：
Rylova SN
影响因子：
9.3
作者：
Rylova, Svetlana N.;Waser, Beatrice;Maecke, Helmut R.
通讯作者：
Maecke, Helmut R.
N-(m-[125I]碘苯基)马来酰亚胺：一种高产率放射性标记抗体的试剂。
DOI：
10.1016/0883-2897(92)90113-d
发表时间：
1992
期刊：
International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology
影响因子：
--
作者：
Khawli,LA;vandenAbbeele,AD;Kassis,AI
通讯作者：
Kassis,AI