Development of novel acyclic chelators for gallium-68 and scandium-44 used in PET

本提案旨在利用镓-68和钪-44制备下一代正电子发射断层扫描（PET）用放射性示踪剂，可在生理条件下快速进行放射性标记，便于转化为临床，使显像剂的生产过程大大加快，使放射药师更容易承担。本项目旨在将新型配体应用于目前用于显像剂生产的临床设备，使这一过程更快、更高效。该项目将为此开发一系列双功能配体，以允许使用镓-68和钪-44对前列腺癌进行成像，并验证最新微流控技术的放射性标记潜力，以便快速转化为用于GMP生产的放射药学应用。这些药物将能够将放射性标签直接带到癌变部位，并允许肿瘤很容易地通过正电子发射断层扫描（PET）成像。利用这些信息，一种相关的载体分子将在对周围组织损害最小的情况下向癌变肿瘤输送放射性有效载荷。该引导系统将包括对癌变肿瘤中过度表达的基序（受体）具有亲和力的肽群。被命名的研究小组之所以被选中，是因为他们在无机化学、生物学、PET成像和微流体技术方面，为KCL和赫尔大学的pi小组提供了互补的专业知识。命名组、临床医生和放射药理学家之间的定期会议/研讨会将确保新药的验证途径。利用当地的科学论坛和博客将使该团队能够与公众和患者接触。该项目将在考虑商业化的情况下进行，并需要尽量减少这些螯合剂设计的复杂性（步骤数），同时还需要优化在“床边”的更广泛利用，即温和的条件和有限的放射性步骤。

This proposal sets out to make the next generation of radiotracers using gallium-68 and scandium-44 for use positron emission tomography (PET), which can be rapidly radiolabelled under physiological conditions for easy translation into the clinic and make the process of production of imaging agent significantly quicker and easier for the radipharmist to undertake. this project is designed to take the novel ligands and apply them to the clinical equipment used currently for production of imaging agents and make this process faster and more efficient. This project will develop a series of bifunctional ligands for this to allow for imaging of prostate cancer using gallium-68 and scandium-44, and validate the radiolabeling potential in the latest microfluidic technology for rapid translation to radiopharmacy use for GMP production.These agents will be capable of taking a radiolabel directly to a cancerous site and allowing the tumour to be easily visualized by positron emission tomography (PET) imaging. Using this information, a related carrier molecule will then deliver a radioactive payload to the cancerous tumour with minimal damage to the surrounding tissue. The guiding system will comprise peptide groups which have an affinity for motifs (receptors) that are overexpressed at the cancerous tumour.The named research groups have been selected given that they contribute complementary expertise to that available in the PIs group at KCL and Hull, with a mix of inorganic chemistry, biology, PET imaging and microfluidic technology. Regular meetings/workshops between the named groups, clinicians and radiopharmacists will ensure a validation pathway for the new agents. Use of local science forums and blogs will enable the team to engage with the public and patients.This project will progress with commercialization in mind and the need to minimise both the complexity (number of steps) of the design of these chelators and also the need to optimize wider utilization at the 'bed-side', i.e. mild conditions and limited radioactive steps.