Bridging Research and Clinical Practice: Automated [68Ga]Ga-FAPi-46 Synthesis and Quality Control for Oncological PET Imaging

Background/Objectives: Fibroblast activation protein (FAP) has emerged as a promising target for oncologic molecular imaging due to its high expression in cancer-associated fibroblasts and low presence in healthy tissues. Among available FAP ligands, [68Ga]Ga-FAPi-46 has shown rapid tumor accumulation, low background uptake, and broad tumor applicability. This study reports the successful translation of [68Ga]Ga-FAPi-46 from preclinical development to routine clinical radiopharmacy practice, detailing automated synthesis, quality control performance, radiochemical stability, and the first clinical imaging results. Methods: Automated radiolabeling of FAPi-46 with gallium-68 was performed using a synthesis module. Quality control included radiochemical purity assessments by iTLC, SPE, and RP-HPLC (pH, appearance, endotoxin levels, and membrane integrity testing). Radiochemical stability was evaluated in saline (up to 6 h) and human serum (up to 90 min). In vitro characterization included the partition coefficient and serum protein binding determination. A clinical evaluation was conducted in a woman with newly diagnosed lung adenocarcinoma who underwent both [18F]FDG PET/CT and [68Ga]Ga-FAPi-46 PET/CT. Results: Automated synthesis of [68Ga]Ga-FAPi-46 achieved a high radiochemical yield (87.9 ± 1.3%) and radiochemical purity greater than 98%. All batches met release specifications for sterility, apyrogenicity, and physicochemical parameters. The radiotracer demonstrated high stability in saline and human serum, with radiochemical purity consistently above 95% at all evaluated time points. The compound showed a hydrophilic profile (LogP = −3.32 ± 0.14) and 40–60% serum protein binding. Clinically, [68Ga]Ga-FAPi-46 PET/CT provided superior lesion delineation compared to [18F]FDG, revealing additional mediastinal, supraclavicular, and brain metastases. Conclusions: [68Ga]Ga-FAPi-46 can be reliably synthesized using automated procedures under routine radiopharmacy conditions, meeting regulatory quality standards and demonstrating excellent stability. Its enhanced lesion detectability compared with [18F]FDG in the first patient case supports its potential value for oncological staging and clinical implementation.