GMP-Compliant Manufacturing of [68Ga]Ga-ATH001 for a Human Microdose Trial Targeting Platelet-Derived Growth Factor Receptor Beta (PDGFRβ)

Background: The use of suitable radiotracers in positron emission tomography (PET) enables non-invasive quantification of tissue biomarkers in patients. Platelet-derived growth factor receptor beta (PDGFRβ) is a key mediator of fibrogenesis and tumour stroma biology, expressed on activated pericytes, fibroblasts, and cancer-associated stromal cells. These features make PDGFRβ an attractive target for imaging pathological tissue remodelling across fibrotic and malignant diseases. Results: Here, we report the development and clinical translation of [ ⁶⁸ Ga]Ga-DOTA-Cys-ATH001 ([ ⁶⁸ Ga]Ga-ATH001), a novel PET tracer targeting PDGFRβ. [ ⁶⁸ Ga]Ga-ATH001 was successfully produced using an automated in-house sequence on the ModularLab PharmTracer synthesis module. The process achieved high radiochemical purity (97 ± 0.4%), specific activity (2.4 ± 0.1 GBq/mg at the time of administration), reproducibility, and batch-to-batch consistency, ensuring suitability for clinical application. Translation into routine GMP production enabled a clinical trial in which [ ⁶⁸ Ga]Ga-ATH001 was administered to participants with liver metastases. Conclusion: A robust, cGMP-compliant automated synthesis of [ ⁶⁸ Ga]Ga-ATH001 has been established, supporting its clinical translation as a novel PDGFRβ-targeting PET tracer for quantitative imaging of fibrogenesis. The ongoing IMAGINE-1 trial will evaluate PDGFRβ-PET for visualization of liver tumour stroma. Together, these applications position [ ⁶⁸ Ga]Ga-ATH001 as a versatile tracer for assessing PDGFRβ-mediated pathophysiology across both fibrotic and oncologic indications. EU Trial registration: ClinicalTrials.gov, NCT, NCT06562361, Registered 14 August 2024, Study Details | NCT06562361 | A Microdose Trial Investigating Binding of [68Ga]Ga-DOTA-CYS-ATH001 in Healthy Subjects and Different Patient Groups. | ClinicalTrials.gov Clinical Trials Information system: CTIS, EU CT 2025-522290-11-00, Registered 29 September 2025, IMAGINE 1 | 2025-522290-11-00 | CTIS.eu