Development of PET radiotracers for imaging miRNA in the brain

Summary

Positron Emission Tomography (PET) imaging of neuroinflammation is a powerful clinical tool in both the diagnosis of neurological conditions and monitoring treatment. PET imaging of neuroinflammation has been pioneered with imaging activated microglia through the increased expression of the translocator protein receptor (TSPO).

However, due to the limitations of TSPO, such as its genetic polymorphism, there is major interest to investigate improved biomarkers for assessing neuroinflammation. Towards this we have identified miRNA-223 as a potential biomarker of neuroinflammation. We have developed an antagomir-223 sequence radiolabelled with fluorine-18 as a PET radiotracer candidate.

Preliminary in vitro studies indicate this radiotracer can selectively bind to miRNA-223. The transport of the radiotracer across the blood-brain-barrier (BBB) was explored with a cell penetrating peptide, RVG 9R and the results from our preliminary evaluation warrant further investigation by: establishing conditions for the formation of the RVG-9R:antagomir-223 complex; and determining whether the in vivo binding of antagomir-223 is specific and if miRNA-223 can be a suitable biomarker of neuroinflammation.

Project aims

This project aims to:

  • Explore different experimental conditions for the formation of the RVG-9R:antagomir-223 complex to enable efficient delivery across BBB;
  • Expand the scope of the radiolabelling strategy by applying different methodologies to radiolabel antagomir-223 sequences;
  • Conduct in vitro preclinical evaluation in neurons and brain tissue to establish selectivity and specificity of the radiolabelled antagomir-223 sequence and its delivery platform;
  • Conduct in vivo preclinical evaluation of the radiolabelled antagomir-223 sequence with PET to determine the biodistribution and metabolic profile;
  • Explore the radiolabelled antagomir-223 in appropriate animal models of neuroinflammation and compare to the results using gold standard TSPO PET imaging.

Contact details

Dr Selena Milicevic Sephton - sms96@medschl.cam.ac.uk

Opportunities

This project is open to applicants who want to do a:

  • PhD