Bridging Research and Clinical Practice: Automated 68GaGa-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, 68GaGa-FAPi-46 has shown rapid tumor accumulation, low background uptake, and broad tumor applicability. This study reports the successful translation of 68GaGa-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 18FFDG PET/CT and 68GaGa-FAPi-46 PET/CT. Results: Automated synthesis of 68GaGa-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, 68GaGa-FAPi-46 PET/CT provided superior lesion delineation compared to 18FFDG, revealing additional mediastinal, supraclavicular, and brain metastases. Conclusions: 68GaGa-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 18FFDG in the first patient case supports its potential value for oncological staging and clinical implementation.