Radiolabeled Cyclic RGD Peptides as Radiotracers for Imaging Tumors and Thrombosis by SPECT.
Radiolabeled Cyclic RGD Peptides as Radiotracers for Imaging Tumors and Thrombosis by SPECT.
复制标题
DOI：
10.7150/thno/v01p0058
复制
发表时间：
2011-01-18
期刊：
影响因子：
12.4
通讯作者：
Liu S
中科院分区：
文献类型：
--
作者：
Zhou Y;Chakraborty S;Liu S
整合素家族是一组跨膜糖蛋白，由19个α亚基和8个β亚基组成，在细胞表面以25种不同的α/β异二聚体组合表达。整合素在许多生理过程中起关键作用，包括细胞附着、增殖、骨重塑和伤口愈合。整联蛋白还有助于病理事件，如血栓形成、动脉粥样硬化、肿瘤侵袭、血管生成和转移、病原微生物感染和免疫功能障碍。在整合素家族的25个成员中，αvβ3因其在肿瘤生长、进展和血管生成中的作用而被最广泛地研究。相反，αIIbβ3仅在血小板上表达，促进细胞间双向信号传导（“由内向外”和“由外向内”），并允许血小板在血管损伤期间聚集。αIIbβ3在血栓形成中起重要作用，其通过活化并与纤维蛋白原结合，特别是在高血流速度引起的动脉血栓形成中。在静息状态下，血小板上的αIIbβ3不与纤维蛋白原结合;在活化状态下，血小板的构象改变，αIIbβ3的结合位点暴露给纤维蛋白原以交联血小板。在过去的二十年中，整合素被认为是诊断和治疗癌症、血栓形成等疾病的分子靶点。最近出现了几篇优秀的综述文章，涵盖了与整合素靶向放射性示踪剂及其在单光子发射计算机断层扫描（SPECT）或正电子发射放射性核素正电子发射断层扫描（PET）肿瘤成像中的核医学应用相关的广泛主题。本文将重点介绍αvβ3靶向放射性示踪剂在肿瘤显像中的最新进展和αIIbβ3靶向放射性示踪剂在血栓显像中的应用，并讨论不同的方法来最大化环RGD肽的靶向能力和改善放射性示踪剂从非癌器官的排泄动力学。靶向摄取和靶向背景比的改善对于靶向特异性放射性示踪剂至关重要。
The integrin family is a group of transmembrane glycoprotein comprised of 19 α- and 8 β-subunits that are expressed in 25 different α/β heterodimeric combinations on the cell surface. Integrins play critical roles in many physiological processes, including cell attachment, proliferation, bone remodeling, and wound healing. Integrins also contribute to pathological events such as thrombosis, atherosclerosis, tumor invasion, angiogenesis and metastasis, infection by pathogenic microorganisms, and immune dysfunction. Among 25 members of the integrin family, the αvβ3 is studied most extensively for its role of tumor growth, progression and angiogenesis. In contrast, the αIIbβ3 is expressed exclusively on platelets, facilitates the intercellular bidirectional signaling (“inside-out” and “outside-in”) and allows the aggregation of platelets during vascular injury. The αIIbβ3 plays an important role in thrombosis by its activation and binding to fibrinogen especially in arterial thrombosis due to the high blood flow rate. In the resting state, the αIIbβ3 on platelets does not bind to fibrinogen; on activation, the conformation of platelet is altered and the binding sites of αIIbβ3 are exposed for fibrinogen to crosslink platelets. Over the last two decades, integrins have been proposed as the molecular targets for diagnosis and therapy of cancer, thrombosis and other diseases. Several excellent review articles have appeared recently to cover a broad range of topics related to the integrin-targeted radiotracers and their nuclear medicine applications in tumor imaging by single photon emission computed tomography (SPECT) or a positron-emitting radionuclide for positron emission tomography (PET). This review will focus on recent developments of αvβ3-targeted radiotracers for imaging tumors and the use of αIIbβ3-targeted radiotracers for thrombosis imaging, and discuss different approaches to maximize the targeting capability of cyclic RGD peptides and improve the radiotracer excretion kinetics from non-cancerous organs. Improvement of target uptake and target-to-background ratios is critically important for target-specific radiotracers.
登录
查看更多内容
影响因子：
6
作者：
Antonov, AS;Kolodgie, FD;Gerrity, RG
通讯作者：
Gerrity, RG
影响因子：
7.3
作者：
BARKER, PL;BULLENS, S;BURNIER, JP
通讯作者：
BURNIER, JP
影响因子：
4.7
作者：
Barrett, JA;Damphousse, DJ;Carroll, TR
通讯作者：
Carroll, TR
DOI：
10.1073/pnas.2234372100
发表时间：
2003-11-25
影响因子：
11.1
作者：
Bakewell, SJ;Nestor, P;Weilbaecher, KN
通讯作者：
Weilbaecher, KN
影响因子：
4.7
作者：
Alves, Susana;Correia, Joao D. G.;Smith, Charles J.
通讯作者：
Smith, Charles J.