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.

项目概要金属具有一系列令人惊叹的特性，可用于生物医学目的，例如金属。铂、钌和铜用于化疗，钇和铟用于放射治疗。钕、铕和铽在铜、镓和整体发光探针中得到应用。许多其他金属同位素可用于 PET 和 SPECT 成像，而钆广泛用于 MRI。锰被提议作为替代品，但是，这些有利的特性是有代价的：风险。金属离子毒性。为了使金属在大多数体内应用中都是安全的，它们必须被紧紧地固定在配位体中。该配体的作用是保护身体免受金属离子的侵害，避免身体的天然金属运输和储存系统并允许金属药物发挥预期作用，但最重要的是这种配体允许。金属离子被排出体外。从广义上讲，金属分为两类之一：1）那些不断进化的生命所接触和吸收的金属优势：2）那些进化中的生命没有接触过且通常不会接触到的矿物质。在生命体中发现：外源金属（其中包括许多重金属）。两类金属离子本质上是不同的，但是它们在生物学上有一个共同的特征：两者都不是异生金属可以被排泄，因为这些途径从未发育过，而必需矿物质则因为这些。它们太有价值了，不能失去。显然，金属离子从施用它们的配体中逃逸代表了一个严重的问题，并且一旦脱离配体，它们就会融入体内，并且永远不会离开。意味着金属和配体之间形成的配合物必须尽可能坚固。一些优秀的配体系统已经在临床医学中使用，但对释放的担忧仍然存在这个小项目的目的是研究这些配体结构中的金属离子是否存在。相对简单，对这些配体系统的修饰将导致显着改善如果是这样，它将为更安全的金属配体系统铺平道路。在生物医学应用中。