Costouros Nick G, Diehn Felix E, Libutti Steven K
Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
J Cell Biochem Suppl. 2002;39:72-8. doi: 10.1002/jcb.10426.
The emergence of angiogenesis as an important target for cancer therapy has led to increased research aimed at understanding the mechanisms underlying the development, maintenance, and destruction of tumor vasculature. Concurrently, molecular imaging technologies have been developed and are being incorporated as integral components of biomedical research due to their ability to noninvasively monitor in vivo molecular events. With the evaluation of numerous anti-angiogenic agents in clinical trials, the adaptation and validation of molecular imaging modalities for monitoring angiogenesis is actively being pursued. The importance of selecting appropriate molecular targets in the study of angiogenesis has become increasingly complex due to the pleiotropy of vascular phenotypes. Furthermore, due to both the relatively low abundance of endothelial cells in tumor tissue and the inherent difficulties of detecting molecular events, molecular imaging of vasculature necessitates continued improvements in achieving higher sensitivity. While several studies have been published that set the groundwork for imaging angiogenesis, much has yet to be accomplished. Various tumor models and transgenic mice provide an excellent resource for developing molecular imaging technologies for the understanding of angiogenesis. This research may play a particularly crucial role in evaluating mechanism and efficacy during pre-clinical testing of anti-angiogenic drugs. Due to practical limitations, however, the implementation of angiogenesis-directed molecular imaging may not extend beyond highly specialized clinical trials. That is, imaging modalities that evaluate angiogenesis at a functional level may prove more appropriate. Despite future technical challenges, molecular imaging will become an important research and clinical tool in evaluating tumor angiogenesis.
血管生成作为癌症治疗的一个重要靶点的出现,引发了更多旨在了解肿瘤血管形成、维持和破坏背后机制的研究。与此同时,分子成像技术已得到发展,并因其能够无创监测体内分子事件而被纳入生物医学研究的重要组成部分。随着众多抗血管生成药物在临床试验中的评估,正在积极探索用于监测血管生成的分子成像模式的适应性和验证。由于血管表型的多效性,在血管生成研究中选择合适分子靶点的重要性变得越来越复杂。此外,由于肿瘤组织中内皮细胞相对丰度较低以及检测分子事件存在固有困难,血管系统的分子成像在实现更高灵敏度方面仍需不断改进。虽然已经发表了几项为血管生成成像奠定基础的研究,但仍有许多工作有待完成。各种肿瘤模型和转基因小鼠为开发用于理解血管生成的分子成像技术提供了极好的资源。这项研究在抗血管生成药物临床前测试期间评估机制和疗效方面可能发挥特别关键的作用。然而,由于实际限制,针对血管生成的分子成像的应用可能不会超出高度专业化的临床试验范围。也就是说,在功能水平上评估血管生成的成像模式可能被证明更合适。尽管未来存在技术挑战,但分子成像将成为评估肿瘤血管生成的重要研究和临床工具。