Novel chelators for Scandium-44 in PET imaging of prostate cancer

用于前列腺癌 PET 成像的新型 Scandium-44 螯合剂

• 批准号: 2904564
• 金额: --
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2904564
• 关键词: Novel; chelators; Scandium; 44; PET

Aim of the PhD Project:Develop new chelators capable of radiolabelling Scandium-44 at room temperature and neutral pHValidate the kinetic stability of the Scandium-44 complexes against biological competitorsDevelop a bifunctional chelator for targeting Scandium-44 in a prostate cancer modelProject description/background:This project sets out to develop the next generation of chelators for scandium-44, which can be rapidly radiolabeled under physiological conditions for facile translation into current technology used within the clinic/radiopharmacy. The development of new chelators that can complex scandium-44 is essential to facilitate translation and widen the scope of applications for these PET radionuclides. Radiolabeling under mild conditions, at neutral pH and low temperatures is important as it will simplify the procedure from radionuclide production to patient by removing multiple synthetic steps currently used in a hospital radiopharmacy or PET centre to produce a tracer for imaging. This will also allow for the use of targeting moieties, such as proteins, that are sensitive to harsh radiolabeling conditions.Scandium-44: 44Sc is a positron emitting isotope which has great potential that is not yet used in clinical PET. With a half-life of 3.9 hours, 44Sc can be used to study longer time course biological processes than Gallium-68, and it can be transported further from the manufacturing site. In addition to this, another isotope of scandium, 47Sc, emits beta- (half-life 3.3 days), and can be used as a therapeutic agent for treatment of cancers. The combination of these two radionuclides would make a powerful theranostic tool: the distribution of the therapeutic agent could be followed exactly using the PET agent. Scandium is thus a versatile radiometal that could be widely used in the future. There is a lack of research into the ligand design for scandium and producing a novel chelator is vital for 44Sc translation into the clinic.In this project we will develop a series of chelators, that show various coordination modes for binding scandium-44, find the ideal system for radiolabeling at neutral pH and kinetic stability, while being able to functionalise with proteins for imaging cancer.We will validate the targeting of these scandium-44 tracers in a prostate cancer model and compare them to the gallium-68 counterparts that are in the clinic.

博士项目的目标：开发能够在室温和中性 pH 值下放射性标记 Scandium-44 的新螯合剂验证 Scandium-44 配合物针对生物竞争对手的动力学稳定性开发一种双功能螯合剂，用于在前列腺癌模型中靶向 Scandium-44 项目描述/背景：该项目着手开发下一代钪44螯合剂，它可以在生理条件下快速进行放射性标记，以便轻松转化为当前使用的技术诊所/放射药剂学。开发能够络合钪-44 的新型螯合剂对于促进这些 PET 放射性核素的转化和扩大应用范围至关重要。在温和条件、中性 pH 值和低温下进行放射性标记非常重要，因为它将简化从放射性核素生产到患者的程序，消除了目前医院放射性制药或 PET 中心用于生产成像示踪剂的多个合成步骤。这也将允许使用对严酷的放射性标记条件敏感的靶向部分，例如蛋白质。Scandium-44: 44Sc 是一种正电子发射同位素，具有巨大的潜力，但尚未用于临床 PET。 44Sc 的半衰期为 3.9 小时，可用于研究比 Gallium-68 更长时程的生物过程，并且可以从生产现场运输到更远的地方。除此之外，钪的另一种同位素47Sc会释放β-（半衰期3.3天），可用作治疗癌症的治疗剂。这两种放射性核素的组合将成为一种强大的治疗诊断工具：使用 PET 试剂可以准确跟踪治疗剂的分布。因此，钪是一种多功能的无线电金属，可以在未来得到广泛的应用。目前缺乏对钪配体设计的研究，生产新型螯合剂对于 44Sc 转化为临床至关重要。在这个项目中，我们将开发一系列螯合剂，展示结合钪-44 的各种配位模式，找到是在中性 pH 值和动力学稳定性下进行放射性标记的理想系统，同时能够与蛋白质一起功能化以进行癌症成像。我们将在前列腺癌模型中验证这些钪 44 示踪剂的靶向性，并将它们与临床上的镓68对应物。