基于放射性示踪剂的血管生成成像策略。
Radiotracer-based strategies to image angiogenesis.
作者信息
Haubner R H, Wester H J, Weber W A, Schwaiger M
机构信息
Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
出版信息
Q J Nucl Med. 2003 Sep;47(3):189-99.
Tumour-induced angiogenesis plays an important role in tumour progression. Great efforts are made to develop therapeutic strategies to interfere with this process resulting in the starvation of the tumour. However, strategies to monitor conventional therapies seems to be inappropriate to control these approaches. Thus, there is a keen interest in developing methods supplying information about the corresponding therapeutical effects. Several radiotracer-based approaches focused on different targets in the angiogenic process are currently investigated. One class of tracers is based on matrix metalloproteinases inhibitors. These compounds show promising results in in vitro assays. However, initial data from in vivo studies using murine tumour models could not confirm successful non-invasive monitoring of MMP activity yet. Another strategy uses a radiolabelled single chain fragment against the ED-B domain of fibronectin, an extracellular matrix protein. Promising results demonstrated selective accumulation of the tracer in the tumour vasculature of a murine tumour model. Most of the studies are concentrated on the development of radiolabelled antagonists of the integrin alpha(v)beta(3). This heterodimeric transmembrane glycoprotein is involved in the migration of activated endothelial cells during formation of new vessels. Different compounds have been labelled with (18F), (111)In, (99m)Tc, (90)Y and several iodine isotopes. In in vitro assays most of them revealed high alpha(v)beta(3) affinity and selectivity. Moreover, in different murine tumour models successful non-invasive determination of alpha(v)beta(3) expression has been shown. Some of these approaches indicate that tumour-induced angiogenesis can be monitored in animal studies. Nevertheless, translation of these approaches into clinical settings allowing visualisation of tumour-induced angiogenesis in patients needs still to be demonstrated.
肿瘤诱导的血管生成在肿瘤进展中起着重要作用。人们付出了巨大努力来开发干扰这一过程的治疗策略,从而使肿瘤饥饿。然而,监测传统疗法的策略似乎不适用于控制这些方法。因此,人们对开发能够提供有关相应治疗效果信息的方法有着浓厚的兴趣。目前正在研究几种基于放射性示踪剂的方法,这些方法聚焦于血管生成过程中的不同靶点。一类示踪剂基于基质金属蛋白酶抑制剂。这些化合物在体外试验中显示出有前景的结果。然而,使用小鼠肿瘤模型的体内研究的初步数据尚未证实对MMP活性进行成功的非侵入性监测。另一种策略使用针对纤连蛋白(一种细胞外基质蛋白)ED-B结构域的放射性标记单链片段。有前景的结果表明该示踪剂在小鼠肿瘤模型的肿瘤血管中选择性积聚。大多数研究集中在整合素α(v)β(3)放射性标记拮抗剂的开发上。这种异二聚体跨膜糖蛋白参与新血管形成过程中活化内皮细胞的迁移。不同的化合物已用(18F)、(111)In、(99m)Tc、(90)Y和几种碘同位素进行标记。在体外试验中,它们中的大多数显示出高α(v)β(3)亲和力和选择性。此外,在不同的小鼠肿瘤模型中已显示成功地非侵入性测定α(v)β(3)表达。其中一些方法表明在动物研究中可以监测肿瘤诱导的血管生成。然而,仍需证明将这些方法转化为临床环境以实现对患者肿瘤诱导血管生成的可视化。