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

PHD项目的目标：开发能够在室温和中性pH下放射性标记Sc-44的新的螯合剂验证Sc-44络合物针对生物竞争者的动力学稳定性在前列腺癌模型中开发用于靶向Sc-44的双功能螯合剂项目描述/背景：该项目致力于开发下一代Sc-44的螯合剂，它可以在生理条件下被快速标记，以方便地转化为当前临床/放射药学中使用的技术。开发能够络合Sc-44的新的螯合剂对于促进这些PET放射性核素的翻译和扩大其应用范围是必不可少的。在温和的条件、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过程，因为它省去了医院放射性药房或PET中心目前使用的多个合成步骤，以生产用于成像的示踪剂。这也将允许使用靶向部分，如对苛刻的放射性标记条件敏感的蛋白质。Sscum-44：44Sc是一种正电子发射同位素，具有巨大的潜力，尚未用于临床PET。与镓-68相比，44Sc的半衰期为3.9小时，可用于研究更长的时间进程生物过程，并且可以运输到离制造现场更远的地方。除此之外，钪的另一种同位素47Sc释放出β-半衰期(半衰期3.3天)，可用作癌症的治疗剂。这两种放射性核素的结合将成为一种强大的治疗工具：使用PET试剂可以准确地跟踪治疗剂的分布。因此，钪是一种用途广泛的放射性金属，在未来可能会得到广泛应用。目前对Sc的配基设计缺乏研究，而生产一种新型的螯合剂对于44Sc转译到临床是至关重要的。在这个项目中，我们将开发一系列螯合剂，显示与Sc-44结合的各种配位模式，在中性pH和动力学稳定性下找到理想的放射性标记系统，同时能够与蛋白质一起用于肿瘤成像。我们将在前列腺癌模型中验证这些Sc-44示踪剂的靶向性，并将它们与临床上的镓-68示踪剂进行比较。

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.