Radiometallated peptides for molecular imaging and targeted therapy
Radiometallated peptides for molecular imaging and targeted therapy
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DOI：
10.1039/c0dt01599g
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发表时间：
2011-01-01
影响因子：
4
通讯作者：
Santos, Isabel
中科院分区：
文献类型：
--
作者：
Correia, Joao D. G.;Paulo, Antonio;Santos, Isabel
在发达国家，癌症是第二大死因，仅次于心血管疾病。开发针对肿瘤的工具以在早期阶段定位和治疗癌症是一个多学科领域，生物学、医学、化学、物理和工程学的融合推动了这一领域的发展。特别是，化学家在这一努力中发挥了关键作用，因为他们不断面临着使用创新的化学策略来开发“智能药物”的挑战。体外观察到，与内源性表达水平相比，某些肿瘤中肽受体过度表达，这促使了将这种受体用作靶点，并设计了基于放射性标记的多肽工具，用于靶向核分子成像和治疗。这种方法在过去20年中获得了越来越多的兴趣，特别是在OctreoScan(R)的成功和对肿瘤组织中调节性多肽受体过度表达的日益了解的推动下。靶向各种疾病相关受体的选定多肽已经到位，并已被不同的放射性金属标记，主要使用双功能方法。本文首先概述了用于标记多肽的金属配位化学的一些相关方面。然后，我们概述了用于核分子成像和/或靶向放射性核素肿瘤治疗的不同家族放射性金属化肽的生物学性能的化学策略。
In developed countries, cancer is the second leading cause of death, being only surpassed by cardiovascular diseases. To develop tumor-targeted tools to localize and treat cancer at an early stage is a multidisciplinary area fuelled by the convergence of biology, medicine, chemistry, physics and engineering. Chemists, in particular, play a critical role in this effort, as they are continuously challenged to use innovative chemical strategies to develop 'smart drugs'. The in vitro observation that peptide receptors are overexpressed in certain tumors, as compared to endogenous expression levels, has prompted the use of such receptors as targets and the design of radiolabelled peptide-based tools for targeted nuclear molecular imaging and therapy. Such approach has gained increased interest over the last two decades, driven in particular by the success of OctreoScan (R) and by the increasing knowledge concerning overexpression of regulatory peptide receptors in tumor tissues. Selected peptides that target a variety of disease related receptors are in place and have been labeled with different radiometals, using mainly the bifunctional approach. This review begins by summarizing some relevant aspects of the coordination chemistry of the metals studied for labeling peptides. Then, we provide an overview of the chemical strategies explored to improve the biological performance of different families of radiometallated peptides for nuclear molecular imaging and/or targeted radionuclide tumor therapy.