Radioiodinated bicyclic RGD peptide for imaging integrin αvβ3 in cancers
Radioiodinated bicyclic RGD peptide for imaging integrin αvβ3 in cancers
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用于癌症整合素 αvβ3 成像的放射性碘标记双环 RGD 肽
DOI：
10.1016/j.bbrc.2020.05.106
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发表时间：
2020
影响因子：
3.1
通讯作者：
Temma Takashi
中科院分区：
文献类型：
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作者：
Kondo Naoya;Wakamori Keita;Hirata Masahiko;Temma Takashi
整合素αvβ 3是肿瘤血管生成的有效标志物，αvβ3特异性成像可以获得关于这一复杂生理过程的重要细节。我们利用新近报道的αvβ3特异性肽双环RGD（bcRGD）作为体内αvβ 3显像探针的基本结构，合成了放射性碘标记的bcRGD，即[125 I]bcRGD，具有高放化纯度（>99%）和高摩尔活性（81 GBq/μmol）。与αvβ 5和α5β 1相比，[125 I]bcRGD对αvβ 3具有更高的选择性。[125 I]bcRGD在αvβ 3高表达的U-87 MG细胞中的蓄积（1.6%剂量/mg）显著高于仅中度表达的A549细胞（0.3%剂量/mg）。此外，给药荷瘤小鼠30 min后，[125 I]bcRGD在U-87 MG肿瘤中的蓄积（3.8% ID/g）显著高于A549肿瘤（2.1% ID/g），U-87 MG肿瘤/血液和U-87 MG肿瘤/肌肉的放射性蓄积比分别为4.0和6.0。这些结果突出了[123/125 I]bcRGD作为体内αvβ 3成像探针的有希望的性质，以及bcRGD作为分子探针的基本结构用于成像和治疗应用的效用。bcRGD可能在未来针对整合素αvβ3相关疾病的治疗诊断学应用中表现出广泛的用途。
Integrin αvβ3is an effective marker of angiogenesis in cancer, and αvβ3-specific imaging can yield important details about this complex physiological process. We utilized the recently reported and highly αvβ3-specific peptide, bicyclic RGD (bcRGD), as the basic structure of anin vivoαvβ3imaging probe, and synthesized a radioiodinated form of bcRGD, namely [125I]bcRGD, with high radiochemical purity (>99%) and high molar activity (81 GBq/μmol). As expected, [125I]bcRGD exhibited high selectivity for αvβ3compared with αvβ5and α5β1in vitro. [125I]bcRGD showed significantly higher accumulation in U-87MG cells (1.6% dose/mg) with high expression of αvβ3compared to A549 cells (0.3% dose/mg) with only moderate expression. Furthermore, 30 min after administration to tumor-bearing mice, [125I]bcRGD showed significantly higher accumulation in U-87MG tumors (3.8% ID/g) than in A549 tumors (2.1% ID/g), and the radioactivity accumulation ratios of U-87MG tumor/blood and U-87MG tumor/muscle were 4.0 and 6.0, respectively. These results highlight the promising properties of [123/125I]bcRGD for use as anin vivoαvβ3imaging probe, as well as the utility of bcRGD as a basic structure of molecular probes for both imaging and therapeutic applications. bcRGD may exhibit broad use in future theranostics applications targeting integrin αvβ3-related diseases.