Tools for the preparation of peptide-based radioligands

用于制备基于肽的放射性配体的工具

• 批准号: RGPIN-2019-05284
• 负责人: Guérin, Brigitte
• 金额: $ 2.11万
• 依托单位: Université de Sherbrooke
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=738169
• 关键词: Tools; preparation; peptide; based; radioligands

Tools for the preparation of peptide-based radioligands Over the past few years, the development of radiopeptides for diagnostic and therapeutic applications in diverse cancers has seen a significant growth. Peptide-based ligands provide many attractive features, including relative ease of preparation by solid phase techniques and accessible chemical diversity utilizing natural and unnatural amino acids. During the last funding period, I implemented new and robust fast-automated purification processes using cassette-based systems for a routine production of radiometals such as 99mTc, 64Cu, 89Zr and 68Ga by cyclotron. As well, convenient approaches to label peptides and antibodies with radiometals via functionalization with both established and novel bifunctional chelators (BFC) were recently developed in my laboratory for 64Cu, 89Zr 68Ga. In continuity with my earlier work, the present proposal advances the development of emerging and highly promising radiometals, such as 45Ti (t½=3.08h) for PET imaging, and 119Sb (t½=38.2h), an Auger-electron emitter that could offer a high therapeutic index along with a second generation of BFCs. I also propose an improved polymer-supported 18F-radiolabelling procedure for the preparation of a variety of 18F-prosthetic groups and 18F-radiopeptides. My long-term objective is to develop an arsenal of innovative tools-radiometals, BFC, polymer-assisted 18F-labelling-that will improve the labelling, molar activity and/or stability of peptide-based radioligands. In addition to developing an arsenal of powerful alternative synthetic tools and procedures dedicated to the preparation and radiolabelling of peptide conjugates, my program will provide a base for the design of new radiopharmaceuticals that will enlarge the number of medical conditions that can benefit from diagnostic PET imaging and targeted radiotherapy. The research proposed herein will also permit the training of HQPs that will possess a unique combination of skills from synthetic chemistry, radiolabelling, biomedical imaging and radiotherapy in an important field of research. This fundamental science program is a unique opportunity for me to develop molecular tools designed to fine-tune the various biological properties of relevant radiolabelled-peptides used for theranostic applications.

在过去的几年中，用于制备基于肽的放射线的工具，在潜水员癌症中开发用于诊断和治疗应用的放射性肽的开发已经显着增长。基于肽的配体提供了许多吸引人的特征，包括使用天然和不自然氨基酸的固相技术相对易于制备以及可访问的化学多样性。在上一个融资期间，我使用基于盒式磁带的系统实施了新的，可靠的快速自动化过程，以常规生产诸如99mtc，64cu，89zr和68GA的辐射量，并通过回旋体进行。同样，最近在我的实验室中开发了64CU，89ZR 68GA的实验室和新型双功能螯合剂（BFC），可通过功能化和新型双功能螯合剂（BFC）标记具有放射线的petides和抗体的方便方法。在我较早的工作中，本提案的发展促进了新兴和高度有希望的辐射量的发展，例如PET成像的45TI（T½= 3.08H），以及119SB（T½= 38.2H），这是一种螺旋螺旋螺旋压 - 电子EMitter，这是一种可以提供高度治疗性索引以及BFC的高度治疗索引。我还提出了一种改进的聚合物支持的18F - 二醇标记程序，用于制备各种18F螺旋型组和18F-二酰胺肽。我的长期目标是开发创新工具标准符的武器，BFC，聚合物辅助18F标签 - 将改善基于肽的放射线的标签，摩尔活性和/或稳定性。除了开发专门用于制备和放射标记肽缀合物的功能强大的替代合成工具和程序外，我的计划还将为设计新的放射性药物的设计提供基础，以增加可以增加诊断宠物成像和靶向放射治疗的医疗状况的数量。本文提出的研究还将允许对HQP进行培训，该培训将在重要的研究领域中从合成化学，放射性标志性，生物医学成像和放射治疗中从合成化学，放射性化成像和放射治疗进行独特的组合。这项基本科学计划是我开发分子工具的独特机会，该工具旨在微调用于疗法应用的相关放射性标记肽的各种生物学特性。