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

Sponsor

Rigshospitalet, Denmark (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT03505346

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Ischemic Heart Disease	Drug: 68Ga-NODAGA-E[c(RGDyK)]2	Phase 2

Detailed 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. Ischemic heart disease is most commently caused by arteriosclerosis of the coronary artery.

If chronic ischemic heart disease is left untreated, it will lead to symptoms to the patient. These symptons occur when the myocardiel oxygen demand exceeds the oxygen provided, due to coronary occlusion.

If the heart suffers from ischemia, 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.

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 before interventions may correlate to recovery of cardiac function and thus serve as a prognostic marker after intervention.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

42 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Jan 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: percutanous coronary intervention(PCI) 200 MBq 68Ga-NODAGA-E[c(RGDyK)]2 administered IV. two times. 14-21 days before intervention and 30-35 days after intervention	Drug: 68Ga-NODAGA-E[c(RGDyK)]2 200 MBq 68Ga-NODAGA-E[c(RGDyK)]2 administered IV. Other Names: RGD-PET
Experimental: Coronary artery bypass-graft(CABG) 200 MBq 68Ga-NODAGA-E[c(RGDyK)]2 administered IV. two times. 14-21 days before intervention and 30-35 days after interventionintervention	Drug: 68Ga-NODAGA-E[c(RGDyK)]2 200 MBq 68Ga-NODAGA-E[c(RGDyK)]2 administered IV. Other Names: RGD-PET

Arm

Intervention/Treatment

Experimental: percutanous coronary intervention(PCI)

200 MBq 68Ga-NODAGA-E[c(RGDyK)]2 administered IV. two times. 14-21 days before intervention and 30-35 days after intervention

Drug: 68Ga-NODAGA-E[c(RGDyK)]2

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

Other Names:

RGD-PET

Experimental: Coronary artery bypass-graft(CABG)

200 MBq 68Ga-NODAGA-E[c(RGDyK)]2 administered IV. two times. 14-21 days before intervention and 30-35 days after interventionintervention

Drug: 68Ga-NODAGA-E[c(RGDyK)]2

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

Other Names:

RGD-PET

Outcome Measures

Primary Outcome Measures

To evaluate myocardial angiogenesis [30-35 days]
Analysing change in uptake of 68Ga-NODAGA-E[c(RGDyK)]2 Positron Emission Tomography after intervention

Secondary Outcome Measures

Correlation between 68Ga-NODAGA-E[c(RGDyK)]2 and myocardial perfusion [30-35 days]
Correlation between uptake of 68Ga-NODAGA-E[c(RGDyK)]2 and change in myocardial perfusion after intervention using Rubidium 82 Positron Emission Tomography
Correlation between 68Ga-NODAGA-E[c(RGDyK)]2 and functional recovery [30-35 days]
Correlation between uptake of 68Ga-NODAGA-E[c(RGDyK)]2 and functional recovery using Magnetic Resonance after intervention
Correlatino between 68Ga-NODAGA-E[c(RGDyK)]2 and viability [30-35 days]
Correlation between uptake of 68Ga-NODAGA-E[c(RGDyK)]2 and viability using Flour-Deoxy-Glucose Positron Emission Tomography after intervention

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age over 50 years
Patient with known chornic ischemic Heart disease admitted to Rigshospitalet to either PCI og CABG

Exclusion Criteria:

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)
Conversion from PCI to CABG
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¨
Type I or II diabetes