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

该提案提出使用镓-68和钪-44制造下一代放射性示踪剂以用于正电子发射断层扫描（PET），其可以在生理条件下快速放射性标记以易于转化到临床中，并且使得放射药剂师进行成像剂的生产过程显著更快和更容易。该项目旨在将新的配体应用于目前用于生产显像剂的临床设备，并使该过程更快和更有效。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进行前列腺癌成像，并验证了最新微流控技术中的放射性标记潜力，可快速转化为GMP生产中的放射性药物用途。这些试剂将能够将放射性标记直接带到癌部位，并使肿瘤易于通过正电子发射断层扫描（PET）可视化。显像利用这些信息，相关的载体分子将在对周围组织损伤最小的情况下向癌性肿瘤输送放射性有效载荷。该指导系统将包含对癌性肿瘤中过表达的基序（受体）具有亲和力的肽组。选定这些研究组是因为它们为KCL和船体的PI组提供了互补的专业知识，并结合了无机化学、生物学、PET成像和微流体技术。指定小组、临床医生和放射性药剂师之间的定期会议/研讨会将确保新药剂的验证途径。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。该项目将考虑商业化以及最大限度地减少这些螯合剂设计的复杂性（步骤数量）以及优化“床边”更广泛使用的需要，即温和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.