Integrin αVβ3-targeted imaging of lung cancer
Integrin αVβ3-targeted imaging of lung cancer
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DOI：
10.1593/neo.04538
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发表时间：
2005-03-01
期刊：
影响因子：
4.8
通讯作者：
Conti, PS
中科院分区：
文献类型：
--
作者：
Chen, XY;Sievers, E;Conti, PS
我们实验室正在开发一系列放射性标记的环状精氨酸-甘氨酸-天冬氨酸（RGD）肽配体，用于细胞粘附分子整合素α（v）β（3）靶向肿瘤血管生成。在本研究中，这项工作继续应用正电子发射器 Cu-64 标记的聚乙二醇化二聚 RGD 肽放射性示踪剂 Cu-64-DOTA-PEG-E[c(RGDyK)](2) 进行肺癌成像。聚乙二醇化的 RGD 肽表明了整合素 α(v)β(3) 亲合力，但与未修饰的 RGD 二聚体相比，聚乙二醇化降低了该配体的受体结合亲和力。放射性示踪剂显示快速的血液清除和主要的肾脏清除途径。正常肺组织和心脏中最小的非特异性活性积累提供了高质量的原位肺癌肿瘤图像，能够清晰划分左肺上叶的原发肿瘤以及纵隔、对侧肺和膈肌的转移瘤。作为比较，对相同小鼠进行的氟脱氧葡萄糖（FDG）扫描只能识别原发性肿瘤，而转移性病变则被强烈的心脏摄取和高肺部背景所掩盖。 Cu-64-DOTA-PEG-E[c(RGDyK)](2) 是一种出色的正电子发射断层扫描 (PET) 示踪剂，用于整合素阳性肿瘤成像。目前正在进行进一步的研究，以提高示踪剂的受体结合亲和力，并随后增加肿瘤摄取的程度，而不影响有利的体内动力学。
A series of radiolabeled cyclic arginine-glycine-aspartic acid (RGD) peptide ligands for cell adhesion molecule integrin alpha(v)beta(3)-targeted tumor angiogenesis targeting are being developed in our laboratory. In this study, this effort continues by applying a positron emitter Cu-64-labeled PEGylated dimeric RGD peptide radiotracer Cu-64-DOTA-PEG-E[c(RGDyK)](2) for lung cancer imaging. The PEGylated RGD peptide indicated integrin alpha(v)beta(3) avidity, but the PEGylation reduced the receptor binding affinity of this ligand compared to the unmodified RGD dimer. The radiotracer revealed rapid blood clearance and predominant renal clearance route. The minimum nonspecific activity accumulation in normal lung tissue and heart rendered high-quality orthotopic lung cancer tumor images, enabling clear demarcation of both the primary tumor at the upper lobe of the left lung, as well as metastases in the mediastinum, contralateral lung, and diaphragm. As a comparison, fluorodeoxyglucose (FDG) scans on the same mice were only able to identify the primary tumor, with the metastatic lesions masked by intense cardiac uptake and high lung background. Cu-64-DOTA-PEG-E[c(RGDyK)](2) is an excellent positron emission tomography (PET) tracer for integrin-positive tumor imaging. Further studies to improve the receptor binding affinity of the tracer and subsequently to increase the magnitude of tumor uptake without comprising the favorable in vivo kinetics are currently in progress.