Molecular Imaging of Plaque Vulnerability

Study Overview
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Brief Summary
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Accumulating data in the literature suggests that radiolabeled-choline (18F-choline) is a sensitive molecular tracer for PET imaging that is taken up in activated cells and, as such, is able to identify active inflammatory sites. The investigators hypothesize that 18F-choline is also highly taken up in vulnerable plaques in comparison to the stable ones.

Detailed Description
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Accumulation and subsequent activation of inflammatory cells in the atherosclerotic plaques play an essential role in transforming a stable plaque into a vulnerable plaque at risk to rupture. On this basis, the study aims to evaluate the diagnostic performance of 18F-choline PET in identifying ongoing inflammation within atherosclerotic plaques. The investigators hypothesize that 18F-choline PET is efficient in detecting intraplaque inflammation and identify vulnerable plaques that are prone to rupture in comparison to the stable ones. It is likely that by correlating the inflammatory status of an atherosclerotic plaque (on 18F-choline PET) with the presence of other vulnerable plaque features (on MR imaging) would be of high clinical relevance for clinical diagnosis of vulnerable plaques.

Official Title
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Molecular Imaging of Plaque Vulnerability Using 18F-choline PET-MRI in Carotid Artery Atherosclerosis Patients

Conditions
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Plaque, Atherosclerotic

Intervention / Treatment
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* Drug: 18F-choline PET-MR imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients known with symptomatic carotid artery stenosis (≥2 mm carotid plaque on duplex ultrasound), who are scheduled in the clinical setting to undergo a carotid endarterectomy or who are referred to conservative therapy; Age 18 years and older (no maximum age); Informed consent by signing informed consent form regarding this study. Exclusion Criteria: Dementia, pregnancy, nursing mothers; Serious neurological deficits at symptomatic side (hemi paralysis, complete aphasia); Severe heart failure NYHA III-IV and severe pulmonary dysfunction dependent on oxygen supply; Patients with contra-indications for MRI (ferromagnetic implants like pacemakers or other electronic implants, metallic splinters in the eyes, vascular clips, claustrophobia, etc.).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 18F-choline PET-MR imaging<br>Intervention: 18F-choline PET-MR imaging. Drug: 18F-choline, dosis 4 MBq/kg body-weight (maximum 360 MBq), administered intravenously as a single dose. Procedure: dynamic and static 18F-choline PET-MR. | Drug: 18F-choline PET-MR imaging<br>* Dynamic and static 18F-choline PET-MR imaging<br>* Other names: PET-MRI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 18F-choline uptake, as marker of plaque inflammation | • To assess on PET the uptake of 18F-choline tracer in the symptomatic carotid artery plaque, given as Target-to-Background uptake Ratio (TBR); | 1 year | 
| correlate the intra-plaque uptake of 18F-choline on PET with the total area of CD68-positivity within the symptomatic plaque | • In case of carotid surgery, to correlate the intra-plaque uptake of 18F-choline on PET with the total area of CD68-positivity within the symptomatic plaque, as a measure of plaque inflammation and vulnerability on histology | 1 year | 
| sensitivity, specificity, negative predictive value of 18F-choline PET | • To determine the sensitivity, specificity, negative predictive value of 18F-choline PET in diagnosis of vulnerable plaques. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of F18-Choline uptake vs other histologic plaque parameters. | • In case of carotid surgery, to correlate the intra-plaque 18F-choline uptake on PET with other histologic plaque parameters besides inflammation, such as the total area of intra-plaque lipid core, haemorrhage, fibrous tissue and calcifications; | 1 year | 
| Correlation of F18-Choline uptake vs PET and MRI parameters of atherosclerotic plaque | • To correlate the intra-plaque 18F-choline uptake on PET and MRI parameters of atherosclerotic plaque, such as % of intra-plaque fibrous tissue, lipid core, hemorrhage, calcifications; | 1 year | 
| Correlation of F18-choline plaque uptake vs 18F-FDG uptake | • To correlate the intra-plaque 18F-choline uptake on PET with the already established FDG PET imaging parameters of atherosclerotic plaque, such as inflammation; | 1 year | 
| Symptomatic vs asymptomatic F18-Choline uptake | • To compare on PET the 18F-choline uptake in the symptomatic carotid plaque with the uptake in the asymptomatic contralateral carotid artery. | 1 year | 
| Correlation of F18choline plaque uptake vs cardiovascular risk profile | • To evaluate a possible association between the degree of 18F-choline uptake on PET with patients' cardiovascular risk profile and medical history. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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18F-fluormethylcholine, [F18] choline, [F18] fluormethylcholine