Optimising radiotracers for in vivo detection of cardiac amyloidosis and monitoring of treatment response

Project ID: 2531bd1655

(You will need this ID for your application)

Research Area(s): chemistry
engineering
physics

UCL Lead department: Division of Medicine

Project Summary:

Advances in diagnostic technology have revealed that transthyretin cardiac amyloidosis (ATTR-CM) is vastly more prevalent than previously thought and could underlie heart failure in 40% of elderly patients. Many novel treatments for ATTR-CM are emerging, making it essential that imaging biomarkers not only detect early signs of disease, but are also sensitive to treatment response.

Interestingly, the mechanisms through which radiotracers detect ATTR-CM are not well understood. Originally designed for detection of bone malignancies, it has been known for decades that ‘bonescan’ tracers accumulate in the hearts of some patients with amyloidosis, but their specificity was thought to be low. Clinical studies from our Centre established a pipeline for nonbiopsy diagnosis of ATTR-CM which has been adopted worldwide. However, multiple different ‘bonescan’ tracers are available (DPD,PYP,HMDP) and their mechanism of detection and sensitivity to treatment are not known, generating an urgent need for preclinical optimisation of this powerful imaging tool.

Given that repeat dosing of patients with different radioactive tracers is unfeasible, we developed a mouse model of ATTR-CM which mimics the clinical phenotype. Your project will utlise in-vivo SPECT-CT to undertake the first direct comparison of the sensitivity of established and novel radiotracers for detecting ATTR-CM, and then track response to treatment. Mouse models allow radiotracer uptake to be directly correlated with molecular, cellular and histological characterisation of pathology. Your research will for the first time shed light on the mechanisms of ATTR-CM detection and ultimately result in a more sensitive and specific diagnostic biomarker which can be used test new therapies and improve treatment of patients.

You will become part of our large team of translational bioengineers, bioimaging scientists and clinicians including Prof. Stuckey’s Cardiovascular Imaging Team at the UCL Centre for Advanced Biomedical Imaging and Profs Fontana and Gillmore’s teams at the National Amyloidosis Centre.