Use of 68Ga-DOTATATE PET to identify the “inflammatory phenotype” in cardiovascular disease: a clinical translational programme (360G-Wellcome-211100_Z_18_Z)
Inflammation drives atherosclerotic plaque rupture underlying most coronary events. While vascular inflammation can be visualised using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), as a glucose analogue this method lacks cell specificity and is unreliable for coronary imaging owing to myocardial signal overspill. My research has shown that 68Ga-DOTATATE, a somatostatin receptor-2 PET ligand, provides a more accurate readout of macrophage-related atherosclerotic inflammation than 18F-FDG, with superior ability to distinguish high-risk versus lower-risk coronary lesions. In three parallel studies, I will test the clinical utility of 68Ga-DOTATATE PET to: i) quantify treatment response to high-intensity lipid-lowering with statins and proprotein convertase subtilisin/kexin type 9 inhibitors in patients with stable cardiovascular disease and familial hypercholesterolaemia; ii) predict disease progression post-myocardial infarction by identifying individuals with "residual" on-treatment coronary arterial inflammation; and iii) diagnose large-vessel vasculitis and monitor treatment response. 68Ga-DOTATATE imaging will also be compared to established MRI, CT, and intravascular imaging markers of atherosclerotic disease severity; and validated in vasculitis using autoradiography, histology and gene expression analyses. Moreover, transcriptomic and epigenetic profiling of monocyte-derived macrophages will be performed to better understand mechanisms underlying residual inflammatory risk defined by 68Ga-DOTATATE. This research will accelerate translation of 68Ga-DOTATATE inflammation imaging to the clinic.
Where is this data from?
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Grant Details
Amount Awarded | 716938 |
Applicant Surname | Tarkin |
Approval Committee | Clinical Interview Committee |
Award Date | 2018-05-23T00:00:00+00:00 |
Financial Year | 2017/18 |
Grant Programme: Title | Clinical Research Career Development Fellowship |
Internal ID | 211100/Z/18/Z |
Lead Applicant | Dr Jason Tarkin |
Partnership Value | 716938 |
Planned Dates: End Date | 2025-04-01T00:00:00+00:00 |
Planned Dates: Start Date | 2019-04-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | East of England |
Sponsor(s) | Dr James Rudd |