Targeting PDGFRβ from radiopharmacy to nuclear medicine: Translational implementation of [68Ga]Ga-ATH001 PET/CT at an academic center.
Abstract
Positron emission tomography (PET) enables non-invasive whole-body assessment of molecular biomarkers and is particularly valuable for evaluating heterogeneous diseases such as cancer. Platelet-derived growth factor receptor beta (PDGFRβ) is a stromal biomarker expressed on activated pericytes and fibroblasts that contributes to tumour remodelling, vascular regulation and therapeutic resistance. This study describes the translational implementation of the PDGFRβ-targeting PET tracer [68Ga]Ga-ATH001, from GMP-compliant radiopharmaceutical development to its first reported oncology application in patients with liver tumours. A GMP-compliant automated synthesis of [68Ga]Ga-ATH001 was established using a ModularLab PharmTracer synthesizer and validated for clinical use. The tracer was prospectively implemented in the IMAGINE-1 study (EU CT 2025-522290-11-00). PET imaging included dynamic liver acquisition immediately after injection, followed by whole-body PET/CT imaging and delayed liver scans to assess tracer biodistribution, tumour uptake and tracer kinetics. [68Ga]Ga-ATH001 was successfully translated into clinical production using an automated in-house synthesis process, achieving a decay-corrected radiochemical yield of 51.9 ± 0.7 %, radiochemical purity of 97 %, radiochemical stability of 96.3 ± 0.5 % after 2 h at room temperature and apparent molar activity of 47.2 ± 1.6 GBq/µmol at EOS. Three consecutive production runs assessed reproducibility; a fourth batch served as a microbiological worst-case challenge and was excluded from the assessment. PET/CT imaging in three patients with colorectal liver metastases showed SUVpeak tumour-to-background ratios of 1.5 to 1.8 at 60 min after injection. GMP-compliant production enabled the first reported oncology application of [68Ga]Ga-ATH001 in patients with liver tumours. The ongoing phase 1 IMAGINE-1 study will further evaluate its clinical potential. Clinical Trials Information system: CTIS, EU CT 2025-522290-11-00, Registered 29 September 2025, IMAGINE-1 | 2025-522290-11-00 | CTIS.eu.
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