Project ID BE-MI2023_16

ThemeBE-MI

Co Supervisor 1A School of Biomedical Engineering & Imaging SciencesWebsite

Co Supervisor 1B School of Biomedical Engineering & Imaging SciencesWebsite

Development of molecular imaging tools to detect cardiac syndrome X.

Background: Coronary microvascular disease (cMVD) is a syndrome characterised by anginal chest pain, fatigue, and shortness of breath. More prevalent in women, it is caused by dysfunction of the smallest vessels in the heart, causing transient diffuse patchy ischaemia. Because no major blood vessels are blocked and there is no contractile dysfunction, it cannot be detected by echocardiography or MRI and is typically diagnosed by excluding all other possibilities (hence “Syndrome X”). We have developed a panel of nuclear molecular imaging approaches which report upon hypoxia (64Cu-bisthiosemicarbazones), mitochondrial dysfunction (99mTc sestamibi & 18F-Mitophos7) and glucose uptake (18FDG), which could positively identify cMVD for the first time.

Aims: We will develop and longitudinally characterise a recently published rodent model of cMVD using the photosensitiser Rose Bengal (Wang JCCM 2019). We will then determine which of our imaging approaches most sensitively identifies the earliest stages of cMVD as a new diagnostic for Syndrome X, and a preclinical (and possibly clinical) platform for developing new drugs and therapies.

Techniques and skills: PET, SPECT, MRI, echocardiography, animal surgery, metabolomics, molecular biology

Objectives: Months 1-6: Assay development and training including ECG, echocardiography, MRI, tissue biomarkers of injury, metabolomics.

Months 6-18: Create and characterise rodent models of cMVD using biomarkers from months 1-6.

Months 12-24: Longitudinal profiling of these models using PET/SPECT, co-validated by the biomarkers from months 1-6.

Months 24-36: Investigate whether PET/SPECT can detect the amelioration of cMVD using statins & ACE inhibitors as a future platform for drug development and personalised medicine.

One representative publication from each co-supervisor:

Detection of anthracycline-induced cardiotoxicity using perfusion-corrected 99mTc sestamibi SPECT Zaitulhusna M. Safee, Friedrich Baark, Edward C. T. Waters, Mattia Veronese, Victoria R. Pell, James E. Clark, Filipa Mota, Lefteris Livieratos, Thomas R Eykyn, Philip J. Blower, Richard Southworth. Scientific Reports 216; 216-227. 2019

64CuCTS: a promising radiopharmaceutical for the identification of low grade cardiac hypoxia by PET Medina, R., Mariotti, E., Pavlovic, D., Shaw, K., Eykyn, T., Blower, P. & Southworth, R., Jun 2015, Journal of Nuclear Medicine. 56, 6, p. 921–926 , 56.