68 Ga-NODAGA-E[c(RGDγK)]2: Positron Emission Tomography Tracer for Imaging of Myocardial Angiogenesis

Acute Myocardial Infarction Clinical Trial

Official title:

68Ga-NODAGA-E[c(RGDγK)]2: a Novel Positron Emission Tomography (PET) Tracer for in Vivo Molecular Imaging of Myocardial Angiogenesis Following Myocardial Infarction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03445884
• Other study ID #: EUDRACR-number: 2017-002709-36
• Status: Completed
• Phase: Phase 2
• Start date: February 20, 2018
• Est. completion date: July 1, 2020

Study information

• Verified date: July 2020
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim is to examine the expression of αvβ3 integrin using a novel selective radiotracer in patients with myocardial infarction and investigate if it is a suitable tool for predicting myocardial recovery and thus prognosis.

Description:

Ischemic heart disease is worldwide the single most frequent cause of death. The number of patients surviving acute myocardial injury is increasing due to improved acute treatment. However, after the initial repair, the tissue undergoes a remodeling phase to compensate for the damaged area. This re-modeling phase can change the structure end geometry of the heart resulting in lower ejection fraction, leading to cardiac dysfunction, which eventually leads to heart failure. Understanding and ideally modifying the reparative mechanisms following myocardial infarction is increasingly important and may lead to improved outcome.

If the heart suffers from ischemia following an acute coronary event, the tissue reacts strongly to the hypoxia. The body will as a compensatory mechanism create new vessel to provide the tissue with oxygen. This is known as the biological process of angiogenesis. This complex process involves different angiogenic and pro-fibrotic transcription factors that initiate the restoration of capillaries by sprouting from the existing endothelial cells in response to hypoxia.

Time seem essential to protect and save the myocardium. An early onset of cytokines and growth factors is associated with a decline in cardiomyocytes apoptosis, smaller infarct areas, and decreased ventricular dilation. Therefore, an early induction of angiogenesis seems important for a good prognosis of the patient.

Integrin αvβ3 is a transmembrane cell surface receptor that is markedly upregulated in states of angiogenesis. It facilitates migration and proliferation and thereby allowing cells to respond to extracellular environment. Integrin αvβ3 is thus a key player in the angiogenic process. The integrin αvβ3 has a binding site for an RGD peptide (Arg-Gly-Asp motif) and this can be targeted by PET tracers.

RGD-based PET tracers have been shown to accumulate at the site of myocardial necrosis in both human and animal studies. The uptake seems to peak a few weeks after the infarction and may correlate to recovery of cardiac function and thus serve as a prognostic marker.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: July 1, 2020
• Est. primary completion date: July 1, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Age over 50 years

Acute myocardial infarction Group:

• Verified first-time acute myocardial infarction treated with PCI

Control Group:

• Previous healthy

• No known cardiac disease

Exclusion Criteria:

• No prior history of acute coronary infarction

• No prior history of Heart surgery

• Not treated with anti-angiogenic medicine

• Subject with pacemaker, cochlear implant or insulin pump

• Pregnancy

• Lactation

• Severe claustrophobia

• Severe obesity (weight above 140kg)

• If a subject is in the fertile age, a pregnancy test will be use prior to injection to the PET_tracer

• If a subject is having a severe allergic reaction to the PET-tracer, the person will be excluded for the rest of the trial

• If the PET-tracer is administered subcutaneous, the person will be excluded for the rest of the trial¨

• Tupe I or II diabetes

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Infarction
• Myocardial Infarction

Intervention

Drug:
• 68Ga-NODAGA-E[c(RGDyK)]2
200 MBq 68Ga-NODAGA-E[c(RGDyK)]2 administered IV.

Locations

Country	Name	City	State
Denmark	Department of Physiology, Nuclear Medicine and PET	Copenhagen	Region Hovedstaden

Sponsors (1)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate myocardial angiogenesis	Analysing uptake of 68Ga-NODAGA-E[c(RGDyK)]2 Positron Emission Tomography in myocardial infarction after PCI	30-35 days
Secondary	Uptake of 68Ga-NODAGA-E[c(RGDyK)]2 and myocardial perfusion	Quantitative uptake of 68Ga-NODAGA-E[c(RGDyK)]2 and change in myocardial perfusion after PCI using Rubidium 82 Positron Emission Tomography after Percutaneous coronary intervention(PCI)	30-35 days
Secondary	Uptake of 68Ga-NODAGA-E[c(RGDyK)]2 and functional recovery	Quantitative uptake of 68Ga-NODAGA-E[c(RGDyK)]2 and functional recovery using Magnetic Resonance after PCI	30-35 days
Secondary	Uptake of 68Ga-NODAGA-E[c(RGDyK)]2 and viability	Quantitative uptake of 68Ga-NODAGA-E[c(RGDyK)]2 and viability using Flour-Deoxy-Glucose Positron Emission Tomography after PCI	30-35 days