Ga-68-Labeled Affibody Molecule-Based Radiopharmaceutical Targeting Platelet Derived Growth Factor Receptor Beta for Detection of Active Fibrosis in Patients with Myocardial Infarction.

Velikyan I, Grinnemo KH, Flodin V, James S, Thelander U, Wagner M, Rodin S, Kero T, Korsgren O, Eriksson O

Pharmaceuticals (Basel, Switzerland) 18 (12) - [2025-12-01; online 2025-12-01]

Introduction: Platelet-derived growth factor receptor beta (PDGFRβ) is a key regulator of fibrogenesis. Non-invasive imaging of PDGFRβ expression may offer a novel approach to assess fibrotic remodeling, particularly in cardiac patients' post-intervention, where fibrosis poses clinical risk. This study presents the GMP-compliant production of a novel PDGFRβ-targeted PET radiopharmaceutical, [68Ga]Ga-DOTA-Z09591 ([68Ga]Ga-ATH001), and its preclinical evaluation in mouse and human myocardial tissue, along with initial clinical imaging in patients with ST-elevation myocardial infarction (STEMI). Methods: The precursor was chemically synthesized and radiolabeled with gallium-68 using a fully automated, GMP-compatible system and a pharmaceutical-grade 68Ge/68Ga generator. Autoradiography, H&E, Sirius Red, Masson's trichrome, and IHC staining were performed on infarcted mouse hearts and human myocardial biopsies. In vivo PET/MRI with [68Ga]Ga-ATH001, 15O-H2O, and gadolinium contrast was conducted in STEMI patients one week post-percutaneous coronary intervention. Results: [68Ga]Ga-ATH001 was produced with high radiochemical yield and purity. Autoradiography demonstrated specific, receptor-mediated binding of [68Ga]Ga-ATH001, co-localizing with PDGFRβ immunoreactivity, collagen deposition, and tissue damage. In STEMI patients, focal tracer uptake was observed in infarcted myocardium correlating with MRI-detected structural abnormalities and perfusion defects on 15O-H2O PET. Uptake in unaffected myocardium was low and homogeneous, consistent with minimal physiological PDGFRβ expression. Conclusions: [68Ga]Ga-ATH001 was successfully developed and validated for phase 0 clinical study. The tracer demonstrated PDGFRβ-specific binding in human fibrotic myocardium and enabled non-invasive detection of myocardial fibrogenic activity in STEMI patients. These findings support further clinical evaluation of [68Ga]Ga-ATH001 as a targeted molecular imaging agent for early assessment of post-infarction fibrosis.

PubMed 41471324

DOI 10.3390/ph18121833

Crossref 10.3390/ph18121833

pmc: PMC12735932
pii: ph18121833