Safer Metal Based Imaging Agents

更安全的金属基显像剂

• 批准号: 10576181
• 负责人: MARK WOODS
• 金额: $ 6.94万
• 依托单位: PORTLAND STATE UNIVERSITY
• 依托单位国家: 美国
• 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/10576181
• 关键词: Biological; Biology; Categories; Chelating Agents; Chemistry; Clinic; Clinical Medicine; Complex; Contrast Media; Copper; Data; Deposition; Diagnostic Imaging; 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; Lead; 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; Wood material; Xenobiotics; Yttrium; arm; base; chemotherapy; clinical application; comparative; design; dietary requirement; effectiveness testing; falls; flexibility; imaging agent; in vivo; interest; intravenous administration; metal chelator; metal complex; prevent; single photon emission computed tomography

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，可用于生物医学目的。金属如 铂、钌和铜用于化疗。钇和铟用于放射治疗。 钕、铕和铽在发光探针中得到应用。铜、镓和全 许多其它金属同位素可用于PET和SPECT成像。钆广泛用于MRI，而 锰被提议作为替代物。然而，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是安全的，它们必须紧紧地保持在配位配体中。目的 这种配体的作用是保护身体免受金属离子的侵害，避免身体自然的金属运输和储存 系统，并允许金属药物按预期发挥作用。但最关键的是，这种配体允许 金属离子被排出。 广义上说，金属可分为两类：1）进化中的生命接触和吸收的金属 优势：重要的矿物质。2）那些进化中的生命没有接触过的， 在生命形式中发现：异生金属（包括许多重金属）。人们可能会认为， 两类金属离子在本质上是不同的，但它们在生物学上有一个共同的特征： 可以排泄。异生物金属，因为这些途径从来没有开发和必需的矿物质， 他们太宝贵了，不能失去 显然，金属离子从它们所施用的配体中逃逸代表了严重的问题， 对人类健康的风险。一旦离开配体，它们就被纳入体内，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坚固。虽然有 一些优秀的配体系统已经在临床医学中使用，关于释放的担忧继续存在 这些配体结构中的金属离子。这个小项目的目的是调查一个小的， 相对简单的，对这些配体系统的修饰将导致在生物活性方面的实质性改善。 复杂的鲁棒性。如果是这样的话，它将为更安全的金属配体系统铺平道路 在生物医学应用中。