PDGFRβ PET imaging to detect cardiac fibrosis after heart attack or in HFpEF

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.

This project will test whether a PET tracer that binds PDGFRβ can spot fibrogenic cells in the hearts of people after a STEMI, in patients with HFpEF, and in healthy volunteers.

Quick facts

• Study type: Observational
• Enrollment: 30 (estimated)
• Ages: 40 Years to 70 Years
• Sex: All
• Sponsor: Uppsala University (Academic / other)
• Locations: 1 site (Uppsala)
• Trial ID: NCT06956560 on ClinicalTrials.gov

What this trial studies

This observational, cross-sectional and longitudinal imaging effort uses a microdose PET tracer ([68Ga]Ga-DOTA-Cys-ATH001) that targets PDGFRβ, a marker of pericyte-derived fibrogenic cells, together with myocardial perfusion PET and gadolinium MRI to map fibrosis-related signals. Four cohorts are enrolled: high-risk STEMI, low-risk STEMI, HFpEF, and healthy controls, with imaging performed on integrated PET/MRI or on separate PET/CT plus MRI systems. Imaging sessions include dynamic myocardial perfusion PET with 15O-H2O, dynamic and static PDGFRβ PET scans, and MRI sequences to measure extracellular volume in infarcted tissue. The goal is to characterize PDGFRβ expression patterns over time and across clinical groups without introducing therapeutic interventions.

Who should consider this trial

Good fit: Ideal candidates are adults aged 40–70 who meet cohort criteria: recent STEMI patients after PCI classified as high- or low-risk by NT-proBNP and TIMI score, patients with HFpEF (EF ≥50% and elevated NT-proBNP), or healthy volunteers willing to undergo PET and MRI scans.

Not a fit: People outside the 40–70 age range, those who do not meet the cohort-specific biomarkers or post-PCI criteria, or individuals unable to undergo PET/MRI (for example due to incompatible implants, severe claustrophobia, pregnancy, or severe renal impairment) are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this approach could allow earlier and more specific detection of fibrotic activity in the heart, improving risk stratification and guiding future targeted therapies.

How similar studies have performed: PDGFRβ-targeted PET imaging is an emerging and mostly preclinical field with limited early human data suggesting promise but not yet widely validated in larger clinical populations.

Eligibility criteria

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.

Where this trial is running

Uppsala

• Uppsala University Hospital — Uppsala, Sweden (Recruiting)

Study contacts

• Principal investigator: Karl-Henrik Grinnemo, MD, PhD — Uppsala University Hospital
• Study coordinator: Karl-Henrik Grinnemo, MD, PhD

Conditions ST-Elevation Myocardial Infarction; Heart Failure With Preserved Ejection Fraction