New Selective PET Imaging Antagonist for the Sphingosine-1-Phosphate Receptors: Novel Biomarkers for Multiple Sclerosis Drug Discovery

该博士研究生的重点是开发一种潜在的PET显像剂，该显像剂将作为鞘氨醇-1受体的选择性拮抗剂。最近在文献中报道的工作已经确定了一类对S1P5具有选择性和拮抗活性的化合物。以这些结构为起点，我们将设计和合成一个小的类似物文库，其中包含一个氟原子，可以进行后期放射性标记。在对这些新化合物进行亲和力的生物测试之后，将研究它们的放射性标记方法。最终，这项研究计划将为多发性硬化症的治疗提供几种潜在的临床应用的新的成像工具，包括对疾病进展的评估、对治疗的反应以及在未来的药物发现计划中的应用。

The focus of this PhD studentship is to develop a potential PET imaging agent that would act as a selective antagonist for the sphingosine-1-receptor. Recent work reported in the literature has identified a class of compounds that show selectivity and antagonist activity for S1P5. Using these structures as a starting point, we will design and synthesise a small library of analogues which incorporate a fluorine atom and that can undergo late-stage radiolabelling. Following biological testing of these novel compounds for affinity, methods for their radiolabelling will then be investigated. Ultimately, this programme of research will deliver new imaging tools with several potential clinical applications for multiple sclerosis treatment, including evaluation of disease progression, response to therapy and application in future drug discovery programmes.