Platelet Derived Growth Factor Receptor ß (PDGFRß) Imaging in Cardiac Fibrosis (PARIS)

Microdosing, Non-randomized, Clinical Trial to Investigate Binding of Positron Emission Tomography Tracer [68ga]Ga-DOTA-Cys-ATH001 Targeting Platelet-derived Growth Factor Receptor Beta (PDGFRß) in Healthy Subject as Compared to Patients With Cardiac Fibrosis.

An observational, cross-sectional, longitudinal, microdosing Position Emission Tomography (PET) imaging study to investigate platelet derived growth factor receptor beta (PDGFRß) expression in the heart of patients with high or low risk of heart failure after a ST-Elevation Myocardial Infarction (STEMI) after a percutaneous coronary intervention (PCI) with a stent procedure, as well as in patients with heart failure with preserved ejection fraction (HFpEF) and healthy individuals.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure With Preserved Ejection Fraction (HFpEF); ST-Elevation Myocardial Infarction (STEMI)
• Intervention / Treatment: Radiation: PET/MRI or separate PET/CT and MRI

Detailed Description

PDGFRß is a biomarker for pericytes which are identified as the progenitor of myofibroblast and fibroblast responsible for extra-cellular matrix proteins deposition in fibrotic heart. The Positron Emission Tomography (PET) tracer [68Ga]Ga-Dodecane tetra acetic acid (DOTA)-Cys-ATH001 is a marker for fibrogenic cells by targeting the surface receptor PDGFRß.

Four cohorts are examined by Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) or separate Positron Emission Tomography/Computed Tomography (PET/CT) and MRI using the following imaging protocol: 15O-H20 (myocardial perfusion, up to 10 min dynamic PET scan), [68Ga]Ga-DOTA-Cys-ATH001 (PDGFRß PET, up to 60 min dynamic + static full body PET scans), and Gd-MRI (extracellular volume in infarct, around 10 min MRI scan).

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Karl-Henrik Grinnemo, MD, PhD; Phone Number: +46186110000; Email: karl-henrik.grinnemo@uu.se

Study Locations

• Sweden
  • Uppsala, Sweden
    • Recruiting
    • Uppsala University Hospital
    • Contact: Karl-Henrik Grinnemo Professor, MD, PhD; Phone Number: +46186110000; Email: karl-henrik.grinnemo@uu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Eligible patients with STEMI high- and low-risk, and HFpEF will be recruited and/or identified from referral sites, by Uppsala University Hospital.

Description

Inclusion Criteria:

• Willing and able to give written informed consent for participation in the trial and able to comply with all trial procedures and requirements.
• Male or female participant aged 40 to 70 years, inclusive, at the screening visit.
• Women of childbearing potential must practice abstinence from heterosexual intercourse or must agree to use a highly effective method of contraception.

Cohort-specific inclusion criteria:

Cohort 1, STEMI high-risk patients:

• NT-proBNP >500 pg/mL within 48 hrs after PCI
• Post-PCI Thrombolysis In Myocardial Infarction (TIMI) score <3.
• No previous history of coronary artery disease or heart failure.

Cohort 2, STEMI low-risk patients

• NT-proBNP <500 pg/mL within 48 hrs after PCI
• Post-PCI TIMI score 3.
• No previous history of coronary artery disease or heart failure.

Cohort 3 (HFpEF patients)

• Presence of signs and symptoms of HF
• Ejection Fraction ≥50%
• Elevated levels of natriuretic peptides (NT-proBNP≥125pg/mL)
• At least one of the following:
• Relevant structural heart disease (left ventricular hypertrophy or left atrial enlargement)
• Diastolic dysfunction

Cohort 4 (healthy participants)

• Individuals with no history of coronary disease or heart failure.
• Medically healthy participant without abnormal clinically significant medical history, physical findings, vital signs, ECG, and laboratory values at the time of the screening visit, as judged by the Investigator.

Exclusion Criteria:

• Any contraindication for MRI according to a standard checklist
• Having worked as a metal worker or welder.
• Contraindication for gadolinium-based contrast agents such as risk of nephrogenic systemic fibrosis (NSF) or allergy to gadolinium.
• Kidney dysfunction measured as estimated Glomerular filtration rate (eGFR)<30 mL/min/1.73m2
• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial or influence the results or the participant's ability to participate in the trial.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the screening visit.
• Any malignancy within the past 12 months before the screening visit, with the exception of successfully treated basal cell carcinoma of the skin or in situ prostate cancer under active surveillance, with no interventions scheduled during the period of trial participation.
• Any active gastrointestinal hemorrhage in the past six months.
• Acute or chronic disabling stroke.
• Aortic aneurysm or aortic dissection.
• Hypertensive crisis.
• Circulatory unstable condition in need for mechanical support.
• Any planned major surgery within the duration of the trial participation.
• Participants who are pregnant, currently breastfeeding, or intend to become pregnant during the course of the trial.
• Poor peripheral venous access, as judged by the Investigator.
• The participant has any laboratory abnormality or condition that, in the Investigator's opinion, could adversely affect the safety of the participant or impair the assessment of trial results.
• The participant is using any prohibited concomitant medications as described in the protocol, at the discretion of the Investigator.
• The Investigator considers the participant unlikely to comply with trial procedures, restrictions, and requirements.

Additional exclusion criteria for all participants (cohorts 1,2 and 4):

• History of coronary artery disease or heart failure.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Individuals with high risk of heart failure after STEMI; Individuals with high risk of heart failure after STEMI are examined by PET using the following imaging protocol: 15O-H20 (myocardial perfusion, up to 10 min dynamic PET scan), [68Ga]Ga-DOTA-Cys-ATH001 (PDGFRß PET, up to 60 min dynamic + static full body PET scans), and Gd-MRI (extracellular volume in infarct, around 10 min MRI scan) at one week after PCI/stent intervention and at 2-8 months after PCI/stent.	Radiation: PET/MRI or separate PET/CT and MRI; PET/MRI or separate PET/CT and MRI using the following imaging protocol: 15O-H20 (myocardial perfusion, up to 10 min dynamic PET scan), [68Ga]Ga-DOTA-Cys-ATH001 (PDGFRß PET, up to 60 min dynamic + static full body PET scans), and Gd-MRI (extracellular volume in infarct, around 10 min MRI scan). Cohort 1 and 2 are examined twice, first one week after PCI/stent and then a second examination 2 to 8 months after the first. Cohorts 3, and 4 are examined once.
Individuals with low risk of heart failure after STEMI; Individuals with low risk of heart failure after STEMI are examined by PET using the following imaging protocol: 15O-H20 (myocardial perfusion, up to 10 min dynamic PET scan), [68Ga]Ga-DOTA-Cys-ATH001 (PDGFRß PET, up to 60 min dynamic + static full body PET scans), and Gd-MRI (extracellular volume in infarct, around 10 min MRI scan) at one week after PCI/stent intervention and at 2-8 months after PCI/stent.	Radiation: PET/MRI or separate PET/CT and MRI; PET/MRI or separate PET/CT and MRI using the following imaging protocol: 15O-H20 (myocardial perfusion, up to 10 min dynamic PET scan), [68Ga]Ga-DOTA-Cys-ATH001 (PDGFRß PET, up to 60 min dynamic + static full body PET scans), and Gd-MRI (extracellular volume in infarct, around 10 min MRI scan). Cohort 1 and 2 are examined twice, first one week after PCI/stent and then a second examination 2 to 8 months after the first. Cohorts 3, and 4 are examined once.
Individuals diagnosed with HFpEF and with signs/symptoms of heart failure; Individuals diagnosed with HFpEF are examined by PET using the following imaging protocol: 15O-H20 (myocardial perfusion, up to 10 min dynamic PET scan), [68Ga]Ga-DOTA-Cys-ATH001 (PDGFRß PET, up to 60 min dynamic + static full body PET scans), and Gd-MRI (extracellular volume in infarct, around 10 min MRI scan) once after inclusion.	Radiation: PET/MRI or separate PET/CT and MRI; PET/MRI or separate PET/CT and MRI using the following imaging protocol: 15O-H20 (myocardial perfusion, up to 10 min dynamic PET scan), [68Ga]Ga-DOTA-Cys-ATH001 (PDGFRß PET, up to 60 min dynamic + static full body PET scans), and Gd-MRI (extracellular volume in infarct, around 10 min MRI scan). Cohort 1 and 2 are examined twice, first one week after PCI/stent and then a second examination 2 to 8 months after the first. Cohorts 3, and 4 are examined once.
Healthy control individuals; Healthy control individuals are examined by PET using the following imaging protocol: 15O-H20 (myocardial perfusion, up to 10 min dynamic PET scan), [68Ga]Ga-DOTA-Cys-ATH001 (PDGFRß PET, up to 60 min dynamic + static full body PET scans), and Gd-MRI (extracellular volume in infarct, around 10 min MRI scan) once after inclusion.	Radiation: PET/MRI or separate PET/CT and MRI; PET/MRI or separate PET/CT and MRI using the following imaging protocol: 15O-H20 (myocardial perfusion, up to 10 min dynamic PET scan), [68Ga]Ga-DOTA-Cys-ATH001 (PDGFRß PET, up to 60 min dynamic + static full body PET scans), and Gd-MRI (extracellular volume in infarct, around 10 min MRI scan). Cohort 1 and 2 are examined twice, first one week after PCI/stent and then a second examination 2 to 8 months after the first. Cohorts 3, and 4 are examined once.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PET-tracer binding in myocardium	Difference in [68Ga]Ga-DOTA-Cys-ATH001 Standardized Uptake Value (SUV)mean / SUVmax / SUVtot in the whole myocardium of healthy subjects compared with STEMI high-risk and low-risk patients, and HFpEF patients.	At PET/MRI baseline, and at PET/MRI at 2-8 months after baseline (cohort 1 and 2)
PET-tracer binding in the infarct	Difference in uptake of [68Ga]Ga-DOTA-Cys-ATH001 in the infarct, as identified by Gd-MRI compared to uptake in healthy myocardium.	At PET/MRI baseline, and at PET/MRI at 2-8 months after baseline (cohort 1 and 2)

Collaborators and Investigators

• Sponsor: Uppsala University
• Investigators: Principal Investigator: Karl-Henrik Grinnemo, MD, PhD, Uppsala University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 25, 2025
• First Submitted That Met QC Criteria: April 25, 2025
• First Posted (Actual): May 4, 2025

Study Record Updates

• Last Update Posted (Actual): August 8, 2025
• Last Update Submitted That Met QC Criteria: August 4, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Necrosis; Myocardial Ischemia; Ischemia; ST Elevation Myocardial Infarction; Myocardial Infarction; Infarction
• Other Study ID Numbers: PARIS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No