Oxygen Sensing, Hypoxia Tracing and in Vivo Imaging with Functional Metalloprobes for the Early Detection of Non-communicable Diseases.
Oxygen Sensing, Hypoxia Tracing and in Vivo Imaging with Functional Metalloprobes for the Early Detection of Non-communicable Diseases.
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DOI：
10.3389/fchem.2018.00027
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发表时间：
2018
影响因子：
5.5
通讯作者：
Pascu SI
中科院分区：
文献类型：
--
作者：
Mirabello V;Cortezon-Tamarit F;Pascu SI
缺氧已被确定为肿瘤环境的标志之一，并且是许多癌症的预后因素。理想的化学探针的发展，缺氧成像和传感仍然难以捉摸。关键特征将包括对生命系统中pO 2的细微变化的可测量响应，以及仅在感兴趣的区域（例如，靶向缺氧组织），同时在体外和体内表现出动力学稳定性。灵敏的探针将包括用于依赖于pO 2的灵敏检测的非传染性疾病（NCD）的成像和治疗的应用平台。只有少数用于缺氧体内成像的探针[主要使用正电子发射断层扫描（PET）]已达到临床研究阶段。许多化合物，虽然呈现出有前途的体外结果作为氧传感探针，但在体内的一般应用方面面临着相当大的缺点。许多缺氧示踪剂的作用机制尚未完全合理化，特别是在金属探针的情况下。对缺氧选择性机制的洞察可以允许优化当前的成像探针候选物，并且这将在此进行探索。在活细胞中氧浓度梯度下的配位化合物的作用模式的机械理解允许向体内应用的化合物的范围的扩展，这反过来将有助于将这些转化为临床应用。本文总结了近年来在发现具有金属配体核的新型氧传感分子方面所做的一些研究工作。我们讨论了它们在体外和/或体内的应用，并对目前应用于临床前和临床设置中缺氧检测和追踪的大量分子成像技术（主要依赖于核医学技术）进行了评价。用于早期诊断的成像/感测探针的设计将长期避免侵入性程序，为各种NCD，特别是癌症的治疗监测提供平台。
Hypoxia has been identified as one of the hallmarks of tumor environments and a prognosis factor in many cancers. The development of ideal chemical probes for imaging and sensing of hypoxia remains elusive. Crucial characteristics would include a measurable response to subtle variations of pO2 in living systems and an ability to accumulate only in the areas of interest (e.g., targeting hypoxia tissues) whilst exhibiting kinetic stabilities in vitro and in vivo. A sensitive probe would comprise platforms for applications in imaging and therapy for non-communicable diseases (NCDs) relying on sensitive detection of pO2. Just a handful of probes for the in vivo imaging of hypoxia [mainly using positron emission tomography (PET)] have reached the clinical research stage. Many chemical compounds, whilst presenting promising in vitro results as oxygen-sensing probes, are facing considerable disadvantages regarding their general application in vivo. The mechanisms of action of many hypoxia tracers have not been entirely rationalized, especially in the case of metallo-probes. An insight into the hypoxia selectivity mechanisms can allow an optimization of current imaging probes candidates and this will be explored hereby. The mechanistic understanding of the modes of action of coordination compounds under oxygen concentration gradients in living cells allows an expansion of the scope of compounds toward in vivo applications which, in turn, would help translate these into clinical applications. We summarize hereby some of the recent research efforts made toward the discovery of new oxygen sensing molecules having a metal-ligand core. We discuss their applications in vitro and/or in vivo, with an appreciation of a plethora of molecular imaging techniques (mainly reliant on nuclear medicine techniques) currently applied in the detection and tracing of hypoxia in the preclinical and clinical setups. The design of imaging/sensing probe for early-stage diagnosis would longer term avoid invasive procedures providing platforms for therapy monitoring in a variety of NCDs and, particularly, in cancers.
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影响因子：
8.8
作者：
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通讯作者：
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影响因子：
6.6
作者：
Cortezon-Tamarit, Fernando;Sarpaki, Sophia;Pascu, Sofia I.
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