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Safer Metal Based Imaging Agents

更安全的金属基显像剂

基本信息

批准号：
10709659
负责人：
MARK WOODS
金额：
$ 6.95万
依托单位：
PORTLAND STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-30 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10709659
关键词：
Biological Biology Categories Chemistry Clinic Clinical Medicine Complex Contrast Media Copper Data Deposition Diagnostic Imaging Electronics Europium Evaluation Evolution Excretory function Gadolinium Gallium Generations Government Hand Health Heavy Metals Hemochromatosis Hemorrhage Hepatolenticular Degeneration Human Indium Ions Iron Overload Isomerism Isotopes Laboratories Libraries Life Ligands Magnetic Resonance Imaging Manganese Manganism Medicine Metals Methodology Methods Minerals Modification Molecular Conformation Neodymium Organism Oxidation-Reduction Pathway interactions Persons Pharmacologic Substance Platinum Poison Positioning Attribute Positron-Emission Tomography Price Process Property Radiation therapy Radio Radioactivity Regulation Risk Risk Factors Ruthenium Structure Sweating System Terbium Testing Toxic effect Xenobiotics Yttrium arm chelation chemotherapy clinical application comparative design dietary requirement effectiveness testing falls flexibility imaging agent improved in vivo interest intravenous administration metal complex prevent single photon emission computed tomography

项目摘要

Project Summary Metals offer a stunning array of properties that can be exploited for biomedical purposes. Metals such as platinum, ruthenium and copper are used in chemotherapy. Yttrium and indium are used in radiotherapy. Neodymium, europium and terbium are finding application in luminescent probes. Copper, gallium and whole host of other metal isotopes can be used in PET and SPECT imaging. Gadolinium is widely used in MRI, while manganese is proposed as an alternative. However, these advantageous properties come with a price: the risk of metal ion toxicity. To make metals safe for most in vivo application they must be held tightly in a coordinating ligand. The purpose of this ligand is to shield the body from the metal ion, avoiding the body’s natural metal transport and storage systems and permit the metallo-pharmaceutical to perform as intended. But most crucially this ligand allows the metal ion to be excreted. Broadly speaking, metals fall into one of two categories: 1) Those to which evolving life was exposed and took advantage: the essential minerals. And 2) those to which evolving life had no exposure and are not normally found in lifeforms: the xenobiotic metals (which includes many of the heavy metals). One might expect that these two classes of metal ion would be fundamentally different, but, they share a common feature in biology: neither can be excreted. Xenobiotic metals because these pathways never developed and essential minerals because they are too valuable to lose. Clearly metal ions escaping from the ligands in which they are administered represents a serious problem and risk to human health. Once out of the ligand they are incorporated into the body and can never leave. This means that the complexes formed between metal and ligand must be as robust as possible. Although there are some excellent ligand systems already in use in clinical medicine, concern continues to exist about the release of metal ions from these ligand structures. The aim of this small project is to investigate whether a small, and comparatively simple, modification to these ligand systems would lead to substantial improvements in the robustness of the complex. If so it will have the effect of paving the way to yet safer ligand systems for metals in biomedical applications.

项目摘要金属提供了一系列令人惊叹的特性，可以用于生物医学目的。金属，如铂、钚和铜被用于化疗。在放射治疗中用到了钇和铟。钕、Eu和Tb在发光探针中得到了应用。铜、镓和全铜其他金属同位素的主体可用于正电子发射计算机断层扫描和SPECT成像。Gd在核磁共振中被广泛使用，而建议将锰作为一种替代品。然而，这些有利的房产是有代价的：风险金属离子毒性。为了使金属对大多数活体应用是安全的，它们必须紧紧地保持在一个配位配体中。目的这种配体的作用是保护身体免受金属离子的伤害，避免人体自然的金属运输和储存系统，并允许金属药物发挥预期的作用。但最关键的是，这种配体允许需要排泄的金属离子。广义地说，金属分为两类：1)进化生命所接触到的金属优势：精华矿物质。2)那些进化的生命没有接触到的，也不是正常的发现于生命形式中：外来金属(包括许多重金属)。人们可能会想到，这些两类金属离子将从根本上不同，但它们在生物学上有一个共同的特征：都不是可以被排泄出来。异种生物金属，因为这些途径从未开发过，而必需矿物质是因为它们太有价值了，不能丢。显然，金属离子从给药的配体中逃逸是一个严重的问题，对人类健康的威胁。一旦离开配体，它们就会结合到体内，永远不能离开。这这意味着金属和配体之间形成的络合物必须尽可能地坚固。尽管有一些优秀的配基系统已经在临床医学中使用，对释放的担忧继续存在这些配基结构中的金属离子。这个小项目的目的是调查一个小的，和相对简单的是，对这些配基系统的修改将导致对复合体的健壮性。如果是这样的话，它将为更安全的金属配体系统铺平道路在生物医学方面的应用。