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

点击翻译按钮获取中文摘要

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.