68Ga-NODAGA-RGD PET in Patients With an Occluded Coronary Artery

Study Overview
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Brief Summary
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Background: In patients with coronary artery disease, acute or chronic coronary artery occlusion is associated with various degrees of ischemic myocardial injury and left ventricle dysfunction. The integrin αVβ3 plays a role in angiogenesis, i.e. formation of new capillaries from pre-existing blood vessels that is increased during repair of ischemic myocardial injury. 68Ga-NODAGA-RGD is a radiopharmaceutical for positron emission tomography (PET) imaging of αVβ3 integrin expression. Aim: This study aims at evaluating the feasibility of imaging myocardial αVβ3 integrin expression using 68-Ga-NODAGA-RGD PET and whether 68Ga-NODAGA-RGD uptake is associated with myocardial contractile function in patients with an acute or chronic coronary artery occlusion. Study design: An academic, prospective, open-label study in 60 patients with an acute or chronic coronary occlusion. Study population: 30 patients with an ST-elevation acute myocardial infarction weeks and left ventricular ejection fraction <50%. 30 patients with planned percutaneous re-opening of a chronic coronary total occlusion and left ventricular ejection fraction <50%. Study procedures: Patients will undergo cardiac 68Ga-NODAGA-RGD PET within 3 to 14 days after an ST-elevation acute myocardial infarction or within 4 weeks before and 2 weeks after planned percutaneous re-opening of chronic coronary total occlusion. Myocardial perfusion reserve will be evaluated in patients with chronic total occlusion by PET. Echocardiography will be performed at the time of PET imaging and repeated 6 months later to evaluate global and regional left ventricle contractile function. Data on relevant cardiovascular clinical history and blood sample will be obtained at imaging visits. Cardiac events will be evaluated after two years. End-points: Primary: Myocardial uptake of 68-Ga-NODAGA-RGD after an acute myocardial infarction or before and after opening of chronic coronary occlusion. Secondary: Global and regional left ventricle systolic function. Blood biomarkers of myocardial injury and heart failure. Myocardial perfusion reserve. Adverse cardiac events including death, myocardial infarction, unstable angina pectoris, repeat revascularization and heart failure hospitalizations.

Detailed Description
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Background: In patients with coronary artery disease, acute or chronic coronary artery occlusion is associated with various degrees of ischemic myocardial injury and left ventricle dysfunction. The integrin αVβ3 plays a role in angiogenesis (Brooks 1994), i.e. formation of new capillaries from pre-existing blood vessels that is increased during repair of ischemic myocardial injury (Meoli 2004, Higuchi 2008, Sherif 2012, Sun 2003, Jenkins 2017). 68Ga-NODAGA-RGD is a radiopharmaceutical for positron emission tomography (PET) imaging of αVβ3 integrin expression (Grönman 2017, Buchegger 2011, Pohle 2012, Gnesin 2017). Aim: This study aims at evaluating the feasibility of imaging myocardial αVβ3 integrin expression using 68-Ga-NODAGA-RGD PET and whether 68Ga-NODAGA-RGD uptake is associated with myocardial contractile function in patients with an acute or chronic coronary artery occlusion. Study design: An investigator-initiated, prospective, open-label study in 60 patients with an acute or chronic coronary occlusion. Study population: 30 patients with an ST-elevation acute myocardial infarction weeks and left ventricular ejection fraction <50%. 30 patients with planned percutaneous re-opening of a chronic coronary total occlusion and left ventricular ejection fraction <50%. Study procedures: Patients will undergo cardiac 68Ga-NODAGA-RGD PET within 3 to 14 days after an ST-elevation acute myocardial infarction or within 4 weeks before and 2 weeks after planned percutaneous re-opening of chronic coronary total occlusion. Myocardial perfusion reserve will be evaluated in patients with chronic total occlusion by PET myocardial perfusion imaging. Complete echocardiography will be performed at the time of PET imaging and repeated 6 months later to evaluate global and regional left ventricle contractile function. Data on relevant cardiovascular clinical history and blood sample will be obtained at imaging visits. Cardiac events will be evaluated after two years. Primary end-point: Myocardial uptake of 68-Ga-NODAGA-RGD after an acute myocardial infarction or before and after opening of chronic coronary occlusion. Secondary end-points: Global and regional left ventricle systolic function. Blood biomarkers of myocardial injury (troponin) and heart failure (pro-BNP). Myocardial perfusion reserve. Adverse cardiac events including death, myocardial infarction, unstable angina pectoris, repeat revascularization and heart failure hospitalizations. Sample size: This is an exploratory study and formal power calculation cannot be performed. Ethical aspects: The study conforms to the World Medical Association Declaration of Helsinki. Written statement will be obtained from the ethics committee (the Ethical Board of the South-Western Finland). Permissions from regulatory authorities (the Finnish Medicines Agency Fimea) and the Turku University Hospital for conducting the study will be obtained. Signed and dated informed consent will be obtained from patients before conducting any study specific procedures.

Official Title
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68Ga-NODAGA-RGD Cardiac PET in Patients With Acute Myocardial Infarction or Chronic Total Coronary Occlusion

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Diagnostic Test: 68Ga-NODAGA-RGD PET-imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ST-elevation acute myocardial infarction within 3-14 days Planned elective percutaneous revascularization of angiographically documented coronary chronic total occlusion (CTO) Left ventricular ejection fraction < 50% when hospitalized for index acute myocardial infarction or within 12 months before planned revascularization of coronary CTO Provision of signed and dated informed consent prior to study specific procedures Exclusion Criteria: Current unstable angina Significant valvular heart disease NYHA IV heart failure symptoms Severe untreated hypertension (>180/110 mmHg) Female not post-menopausal Contraindications for adenosine infusion (in patients with CTO): Severe renal failure (estimated glomerular filtration rate < 30 ml/min) Atrial fibrillation with ventricular response > 110 bpm No acoustic window for left ventricle assessment by echocardiography Previous cardiac surgery

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Acute ST-elevation myocardial infarction or chronic coronary artery occlusion<br>68-Ga-NODAGA-RGD PET after acute ST-elevation myocardial infarction or before and after re-opening of a chronic coronary artery occlusion | Diagnostic Test: 68Ga-NODAGA-RGD PET-imaging<br>* Patients will undergo cardiac 68Ga-NODAGA-RGD PET in order to detect myocardial αVβ3 integrin expression 3-14 days after an acute myocardial infarction or within 4 weeks before and 2 weeks after re-opening of chronic coronary occlusion. Echocardiography of cardiac function will be performed at the time of PET imaging and repeated 6 months later.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial uptake of 68Ga-NODAGA-RGD after acute myocardial infarction | 68Ga-NODAGA-RGD uptake in PET images in the myocardial territory supplied by the occluded coronary artery vs. remote myocardium after an acute myocardial infarction | 3 to 14 days after acute myocardial infarction | 
| Myocardial uptake of 68Ga-NODAGA-RGD before and after opening of chronic coronary occlusion | Change in 68Ga-NODAGA-RGD uptake in PET images in the myocardial territory supplied by the occluded coronary artery before and after opening of a chronic coronary occlusion | Within 4 weeks before and 2 weeks after re-opening of a chronic coronary occlusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global left ventricle systolic function | Left ventricle ejection fraction (%) assessed by echocardiography | At the time of 68Ga-NODAGA-RGD PET imaging and after 6 months of follow-up | 
| Regional left ventricle systolic function | Regional myocardial strain (%) assessed by echocardiography | At the time of 68Ga-NODAGA-RGD PET imaging and after 6 months of follow-up | 
| Myocardial perfusion reserve | Assessed by PET myocardial perfusion imaging before and after re-opening of chronic coronary occlusion | At the time of 68Ga-NODAGA-RGD PET imaging within 4 weeks before and 2 weeks after re-opening of a chronic coronary occlusion | 
| Adverse cardiac events | Number of patients with myocardial infarction, unstable angina pectoris, repeat revascularization, heart failure hospitalization or death | After 2 years of follow-up | 
| Blood biomarker of heart failure | pro-BNP (ng/L) | At the time of 68Ga-NODAGA-RGD PET imaging and after 6 months of follow-up | 
| Blood biomarker of myocardial injury | Cardiac troponin T (ng/L) | At the time of 68Ga-NODAGA-RGD PET imaging and after 6 months of follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myocardial Infarction, Positron Emission Tomography