While 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging has been used as an early marker of drug efficacy in numerous clinical cardiovascular drug trials, as a glucose analog, its signal in the vasculature lacks inflammatory cell-specificity. Moreover, high background 18F-FDG signals from the myocardium often preclude coronary artery imaging, despite attempts to suppress myocardial tracer uptake by dietary manipulation. These limitations of 18F-FDG for measuring changes in vascular inflammation arising from drug intervention highlight important unmet needs, which might be overcome by using a somatostatin receptor subtype-2 (SST2) PET tracer.
Up-regulation of SST2 in activated macrophages represents a novel imaging target for measuring vascular inflammation, which has been previously examined in atherosclerosis using 68Ga-DOTATATE. To test the hypothesis that 68Ga-DOTATATE can quantify drug-induced changes in arterial inflammation, patients with primary hypercholesterolaemia (non-familial or familial) or mixed dyslipidaemia with stable cardiovascular Disease (CVD) and elevated LDL cholesterol ≥2.6 despite maximum tolerated statins with or without other lipid lowering therapies will undergo carotid artery 68Ga-DOTATATE PET-magnetic resonance imaging (MRI) in a randomised, double-blind, placebo-controlled study of inclisiran or colchicine. In parallel, we will examine a novel method for detecting plaque composition based on analysis of ultrasound centre frequency shifts, which was developed by collaborators in Lund University, Sweden. The Ultrasound Plaque Structure Analysis (UPSA) method uses radiofrequency algorithms to create real-time tissue-like maps of carotid plaques. Participants in the study will undergo carotid ultrasound imaging using the UPSA method in addition to PET/MRI.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
DIAGNOSTIC
Masking
QUADRUPLE
Enrollment
63
Inclisiran 284 mg, one injection
68Ga-DOTATATE PET-MRI at baseline and 12 weeks
Colchicine 500 mcg tablet once daily
University of Cambridge
Cambridge, United Kingdom
RECRUITINGCarotid 68Ga-DOTATATE PET
Relative change from baseline in carotid artery 68Ga-DOTATATE tissue-to-blood ratio in the index vessel
Time frame: 12 weeks
Carotid UPSA imaging
Relative change from baseline in carotid artery UPSA signal in the index vessel
Time frame: 12 weeks
MRI plaque burden
Relative change from baseline in carotid artery total plaque burden and lipid-rich necrotic core measured by MRI
Time frame: 12 weeks
Carotid 68Ga-DOTATATE vs. serum lipids
Comparison of carotid 68Ga-DOTATATE imaging to serum lipids
Time frame: 12 weeks
Carotid 68Ga-DOTATATE vs. hsCRP
Comparison of carotid 68Ga-DOTATATE imaging to high-sensitivity C-reactive protein (hsCRP)
Time frame: 12 weeks
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