Wu Yun, Cai Weibo, Chen Xiaoyuan
Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University School of Medicine, 1201 Welch Rd, P095, Stanford, CA 94305-5484, USA.
Mol Imaging Biol. 2006 Jul-Aug;8(4):226-36. doi: 10.1007/s11307-006-0041-8.
Cell adhesion molecule integrin alpha v beta 3 is an excellent target for tumor interventions because of its unique expression on the surface of several types of solid tumor cells and on almost all sprouting tumor vasculatures. Here, we describe the development of near-infrared (NIR) fluorochrome Cy7-labeled RGD peptides for tumor integrin targeting.
Mono-, di-, and tetrameric RGD peptides were synthesized and conjugated with Cy7. The integrin specificity of these fluorescent probes was tested in vitro for receptor binding assay and fluorescence microscopy and in vivo for subcutaneous U87MG tumor targeting.
The tetrameric RGD peptide probe with the highest integrin affinity showed the highest tumor activity accumulation and strongest tumor-to-normal tissue contrast. This uptake is integrin-specific as the signal accumulated in the tumor can be effectively blocked by unconjugated RGD peptide antagonist of integrin alpha v beta 3.
Noninvasive NIR fluorescence imaging is able to detect and semiquantify tumor integrin expression based upon the highly potent tetrameric RGD peptide probe.
细胞黏附分子整合素αvβ3是肿瘤干预的理想靶点，因为它在多种实体瘤细胞表面以及几乎所有新生肿瘤血管上均有独特表达。在此，我们描述了用于肿瘤整合素靶向的近红外（NIR）荧光染料Cy7标记的RGD肽的研发情况。
合成了单聚体、二聚体和四聚体RGD肽，并与Cy7偶联。这些荧光探针的整合素特异性在体外进行了受体结合测定和荧光显微镜检测，在体内进行了皮下U87MG肿瘤靶向检测。
整合素亲和力最高的四聚体RGD肽探针显示出最高的肿瘤活性积累和最强的肿瘤与正常组织对比度。这种摄取具有整合素特异性，因为肿瘤中积累的信号可被整合素αvβ3的未偶联RGD肽拮抗剂有效阻断。
基于高效四聚体RGD肽探针，非侵入性近红外荧光成像能够检测并半定量肿瘤整合素表达。
