Work

Fully automated [68Ga]Ga-FAPI-46 radiosynthesis using GalliAd® generator and MiniAIO® synthesizer: development and validation for PET imaging of fibroblast activation protein

Year: 2026

Type: article

Abstract: Background: Fibroblast activation protein (FAP) is a membrane-bound serine protease that is selectively overexpressed on cancer-associated fibroblasts (CAFs) in more than 90% of epithelial tumours. [68Ga]Ga labelled FAP inhibitors (FAPI) have emerged as promising PET tracers for oncological imaging and theranostic applications. [68Ga]Ga-FAPI-46 is a DOTA-chelated FAPI that demonstrates superior tumour retention compared to earlier FAPI compounds. We describe the development, optimisation, and pharmaceutical validation of a combination not previously reported for the production of this radiopharmaceutical: a semi-automated, one-step radiosynthesis of [68Ga]Ga-FAPI-46 without pre-purification of the generator eluate, performed at the hospital radiopharmacy of the Groupement Hospitalier Sud, Hospices Civils de Lyon, in the context of a clinical trial (EudraCT 2025-524897-40-00). Radiolabelling was performed via a miniAIO automated synthesizer (Trasis) and a GalliAd [68Ge]/[68Ga] generator (IRE-Elit). The process - generator elution, direct radiolabelling at 95°C for 7 min in acetate buffer with L-ascorbic acid, HLB solid-phase purification and 0.22 μm sterilizing filtration - was performed in a single uninterrupted automated sequence. The quality control testings included release tests (visual appearance, final volume, radioactivity, pH, radiochemical purity by radio-TLC and radio-HPLC, radionuclidic identity, filter integrity, and bacterial endotoxin testing), post-release tests (radionuclidic purity and sterility), and validation batch-only tests (L-ascorbic acid and ethanol content). Analytical methods were validated as per ICH Q2(R2). Results: All the validation batches met the predefined release and post-release specifications. The decay-corrected radiochemical yields ranged from 71.0% to 91.1%, with a total synthesis time of 20 min. Radiochemical purity exceeded 99.6% by radio-TLC and reached 100% by radio-HPLC at release, stayed ≥ 99.5% after 3 hours. No radiolytic impurities were detected. Radionuclidic purity was confirmed with [68Ge]Ge breakthrough <0.001%, and the measured half-life values (66–67 min) were consistent with those of [68Ga]Ga. Endotoxin levels were <1.0 IU/mL and all batches were sterile. Ethanol (5.4–7.1% v/v) and L-ascorbic acid (8.1–8.6 g/L) contents complied with predefined specifications. All analytical methods fulfilled the ICH Q2(R2) criteria, demonstrating adequate specificity, sensitivity and reproducibility. Conclusions: A fully validated one-step automated radiosynthesis of [68Ga]GaFAPI46 was established via the use of a miniAIO synthetiser with a [68Ge]/[68Ga] generator. The process consistently produced a high-quality radiopharmaceutical suitable for clinical implementation and IMP submission in FAP-targeted PET imaging. Trial registration : EudraCT No: 2025-524897-40-00; Clinical trials registry: NCT07313033 ; 15/01/2026.

Source: EJNMMI Radiopharmacy and Chemistry

DOI: 10.1186/s41181-026-00488-2