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

NCT04871217 | Unknown

• 1 other identifier: T02/011/18
• Study Type: interventional
• Target: 60
• Locations: 3 countries
• Sites: 3

Brief Summary

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.

Conditions

Coronary Artery Disease

Keywords

Positron Emission Tomography; Myocardial Infarction

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Global left ventricle systolic function

  At the time of 68Ga-NODAGA-RGD PET imaging and after 6 months of follow-up

• Regional left ventricle systolic function

  At the time of 68Ga-NODAGA-RGD PET imaging and after 6 months of follow-up

• Myocardial perfusion reserve

  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

  After 2 years of follow-up

• Blood biomarker of heart failure

  At the time of 68Ga-NODAGA-RGD PET imaging and after 6 months of follow-up

Study Arms (1)

Acute ST-elevation myocardial infarction or chronic coronary artery occlusion

EXPERIMENTAL

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

Interventions

68Ga-NODAGA-RGD PET-imaging DIAGNOSTIC_TEST

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.

Acute ST-elevation myocardial infarction or chronic coronary artery occlusion

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Turku University Hospital: lead
• University of Lausanne Hospitals: collaborator
• Leiden University Medical Center: collaborator

Study Sites (3)

Turku University Hospital

Turku, 20520, Finland

RECRUITING

Leiden Medical Center

Leiden, Netherlands

ACTIVE NOT RECRUITING

University of Lausanne Hospitals

Lausanne, CH-1011, Switzerland

RECRUITING

Related Publications (11)

• Brooks PC, Clark RA, Cheresh DA. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science. 1994 Apr 22;264(5158):569-71. doi: 10.1126/science.7512751.

  PMID: 7512751 BACKGROUND

• Buchegger F, Viertl D, Baechler S, Dunet V, Kosinski M, Poitry-Yamate C, Ruegg C, Prior JO. 68Ga-NODAGA-RGDyK for alphavbeta3 integrin PET imaging. Preclinical investigation and dosimetry. Nuklearmedizin. 2011;50(6):225-33. doi: 10.3413/Nukmed-0416-11-06. Epub 2011 Oct 11.

  PMID: 21989840 BACKGROUND

• Gronman M, Tarkia M, Kiviniemi T, Halonen P, Kuivanen A, Savunen T, Tolvanen T, Teuho J, Kakela M, Metsala O, Pietila M, Saukko P, Yla-Herttuala S, Knuuti J, Roivainen A, Saraste A. Imaging of alphavbeta3 integrin expression in experimental myocardial ischemia with [68Ga]NODAGA-RGD positron emission tomography. J Transl Med. 2017 Jun 19;15(1):144. doi: 10.1186/s12967-017-1245-1.

  PMID: 28629432 BACKGROUND

• Higuchi T, Bengel FM, Seidl S, Watzlowik P, Kessler H, Hegenloh R, Reder S, Nekolla SG, Wester HJ, Schwaiger M. Assessment of alphavbeta3 integrin expression after myocardial infarction by positron emission tomography. Cardiovasc Res. 2008 May 1;78(2):395-403. doi: 10.1093/cvr/cvn033. Epub 2008 Feb 6.

  PMID: 18256073 BACKGROUND

• Jenkins WS, Vesey AT, Stirrat C, Connell M, Lucatelli C, Neale A, Moles C, Vickers A, Fletcher A, Pawade T, Wilson I, Rudd JH, van Beek EJ, Mirsadraee S, Dweck MR, Newby DE. Cardiac alphaVbeta3 integrin expression following acute myocardial infarction in humans. Heart. 2017 Apr;103(8):607-615. doi: 10.1136/heartjnl-2016-310115. Epub 2016 Dec 7.

  PMID: 27927700 BACKGROUND

• Meoli DF, Sadeghi MM, Krassilnikova S, Bourke BN, Giordano FJ, Dione DP, Su H, Edwards DS, Liu S, Harris TD, Madri JA, Zaret BL, Sinusas AJ. Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction. J Clin Invest. 2004 Jun;113(12):1684-91. doi: 10.1172/JCI20352.

  PMID: 15199403 BACKGROUND

• Pohle K, Notni J, Bussemer J, Kessler H, Schwaiger M, Beer AJ. 68Ga-NODAGA-RGD is a suitable substitute for (18)F-Galacto-RGD and can be produced with high specific activity in a cGMP/GRP compliant automated process. Nucl Med Biol. 2012 Aug;39(6):777-84. doi: 10.1016/j.nucmedbio.2012.02.006. Epub 2012 Mar 22.

  PMID: 22444238 BACKGROUND

• Sherif HM, Saraste A, Nekolla SG, Weidl E, Reder S, Tapfer A, Rudelius M, Higuchi T, Botnar RM, Wester HJ, Schwaiger M. Molecular imaging of early alphavbeta3 integrin expression predicts long-term left-ventricle remodeling after myocardial infarction in rats. J Nucl Med. 2012 Feb;53(2):318-23. doi: 10.2967/jnumed.111.091652.

  PMID: 22302965 BACKGROUND

• Sun M, Opavsky MA, Stewart DJ, Rabinovitch M, Dawood F, Wen WH, Liu PP. Temporal response and localization of integrins beta1 and beta3 in the heart after myocardial infarction: regulation by cytokines. Circulation. 2003 Feb 25;107(7):1046-52. doi: 10.1161/01.cir.0000051363.86009.3c.

  PMID: 12600920 BACKGROUND

• Gnesin S, Mitsakis P, Cicone F, Deshayes E, Dunet V, Gallino AF, Kosinski M, Baechler S, Buchegger F, Viertl D, Prior JO. First in-human radiation dosimetry of 68Ga-NODAGA-RGDyK. EJNMMI Res. 2017 Dec;7(1):43. doi: 10.1186/s13550-017-0288-x. Epub 2017 May 18.

  PMID: 28523582 BACKGROUND

• Nammas W, Paunonen C, Teuho J, Siekkinen R, Luoto P, Kakela M, Hietanen A, Viljanen T, Dietz M, Prior JO, Li XG, Roivainen A, Knuuti J, Saraste A. Imaging of Myocardial alphavbeta3 Integrin Expression for Evaluation of Myocardial Injury After Acute Myocardial Infarction. J Nucl Med. 2024 Jan 2;65(1):132-138. doi: 10.2967/jnumed.123.266148.

  PMID: 37973184 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Myocardial Infarction

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Study Officials

• Antti Saraste, MD, PhD

  Turku University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Antti Saraste, MD, PhD

CONTACT

+35823130000; antti.saraste@utu.fi

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: January 14, 2021
• First Posted: May 4, 2021
• Study Start: December 4, 2018
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: March 22, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1); FI (1); NL (1)