Department of Nuclear Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Cancer Biother Radiopharm. 2009 Dec;24(6):637-47. doi: 10.1089/cbr.2009.0694.
Angiogenesis is a multistep process regulated by pro- and antiangiogenic factors. In order to grow and metastasize, tumors need a constant supply of oxygen and nutrients. For growth beyond 1-2 mm in size, tumors are dependent on angiogenesis. Inhibition of angiogenesis is a new cancer treatment strategy that is now widely investigated clinically. Researchers have begun to search for objective measures that indicate pharmacologic responses to antiangiogenic drugs. Therefore, there is a great interest in techniques to visualize angiogenesis in growing tumors noninvasively. Several markers have been described that are preferentially expressed on newly formed blood vessels in tumors (alpha(v)beta(3) integrin, vascular endothelial growth factor, and its receptor, prostate-specific membrane antigen) and in the extracellular matrix surrounding newly formed blood vessels (extra domain B of fibronectin, Tenascin-C, matrix metalloproteinases, and Robo-4). Several ligands targeting these markers have been tested as a radiotracer for imaging angiogenesis in tumors. The potential of some of these tracers, such as radiolabeled cyclic RGD peptides and radiolabeled anti-PSMA antibodies, has already been tested in cancer patients, while for markers such as Robo-4, the ligand has not yet been identified. In this review, an overview on the currently used nuclear imaging probes for noninvasive visualization of tumor angiogenesis is given.
血管生成是一个受促血管生成和抗血管生成因子调节的多步骤过程。为了生长和转移，肿瘤需要持续供应氧气和营养物质。对于大小超过 1-2 毫米的肿瘤，生长依赖于血管生成。抑制血管生成是一种新的癌症治疗策略，目前正在临床上广泛研究。研究人员已经开始寻找能够客观反映抗血管生成药物药效的指标。因此，人们对能够非侵入性地可视化生长中肿瘤血管生成的技术非常感兴趣。已经描述了几种在肿瘤中新形成的血管（α(v)β(3)整合素、血管内皮生长因子及其受体前列腺特异性膜抗原）和新形成的血管周围的细胞外基质（纤维连接蛋白的外显子 B、Tenascin-C、基质金属蛋白酶和 Robo-4）中优先表达的标记物。已经测试了几种针对这些标记物的配体作为示踪剂，以用于成像肿瘤中的血管生成。一些示踪剂的潜力，如放射性标记的环状 RGD 肽和放射性标记的抗 PSMA 抗体，已经在癌症患者中进行了测试，而对于 Robo-4 等标记物，尚未确定其配体。在这篇综述中，概述了目前用于非侵入性可视化肿瘤血管生成的核医学成像探针。
