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

这项提议旨在使使用正电子发射断层扫描(PET)的下一代放射性示踪剂使用-68和Sc-44，这种示踪剂可以在生理条件下快速标记，便于移植到临床，并使显像剂的生产过程显著加快，更易于放射药剂师进行。该项目旨在将新型配体应用于目前用于生产显像剂的临床设备，并使这一过程更快、更有效。该项目将为此开发一系列双功能配体，以使用镓-68和钪-44对前列腺癌进行成像，并在最新的微流控技术中验证放射性标记的潜力，以快速转化为放射性药物用于生产GMP。这些试剂将能够将放射性标记直接带到癌症部位，并使肿瘤易于通过正电子发射断层扫描(PET)成像。利用这一信息，相关的载体分子将向癌症肿瘤运送放射性有效载荷，对周围组织的损害最小。该指导系统将包括对癌症肿瘤中过度表达的基序(受体)具有亲和力的多肽基团。之所以选择命名的研究小组，是因为它们为KCL和赫尔的PIS小组提供的补充专业知识，结合了无机化学、生物学、PET成像和微流控技术。指定的小组、临床医生和放射药剂师之间的定期会议/研讨会将确保新药物的验证途径。使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。该项目的进展将考虑到商业化，并需要将这些螯合剂设计的复杂性(步骤数)降至最低，同时也需要优化“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.