Impact of FAPI-46/dual-tracer PET/CT imaging on radiotherapeutic management in esophageal cancer.

BACKGROUND: Fibroblast activation protein (FAP) is expressed in the tumor microenvironment (TME) of various cancers. In our analysis, we describe the impact of dual-tracer imaging with Gallium-68-radiolabeled inhibitors of FAP (FAPI-46-PET/CT) and fluorodeoxy-D-glucose (FDG-PET/CT) on the radiotherapeutic management of primary esophageal cancer (EC). METHODS: 32 patients with EC, who are scheduled for chemoradiation, received FDG and FAPI-46 PET/CT on the same day (dual-tracer protocol, 71%) or on two separate days (29%) We compared functional tumor volumes (FTVs), gross tumor volumes (GTVs) and tumor stages before and after PET-imaging. Changes in treatment were categorized as "minor" (adaption of radiation field) or "major" (change of treatment regimen). Immunohistochemistry (IHC) staining for FAP was performed in all patients with available tissue. RESULTS: Primary tumor was detected in all FAPI-46/dual-tracer scans and in 30/32 (93%) of FDG scans. Compared to the initial staging CT scan, 12/32 patients (38%) were upstaged in nodal status after the combination of FDG and FAPI-46 PET scans. Two lymph node metastases were only visible in FAPI-46/dual-tracer. New distant metastasis was observed in 2/32 (6%) patients following FAPI-4 -PET/CT. Our findings led to larger RT fields ("minor change") in 5/32 patients (16%) and changed treatment regimen ("major change") in 3/32 patients after FAPI-46/dual-tracer PET/CT. GTVs were larger in FAPI-46/dual-tracer scans compared to FDG-PET/CT (mean 99.0 vs. 80.3 ml, respectively (p < 0.001)) with similar results for nuclear medical FTVs. IHC revealed heterogenous FAP-expression in all specimens (mean H-score: 36.3 (SD 24.6)) without correlation between FAP expression in IHC and FAPI tracer uptake in PET/CT. CONCLUSION: We report first data on the use of PET with FAPI-46 for patients with EC, who are scheduled to receive RT. Tumor uptake was high and not depending on FAP expression in TME. Further, FAPI-46/dual-tracer PET had relevant impact on management in this setting. Our data calls for prospective evaluation of FAPI-46/dual-tracer PET to improve clinical outcomes of EC.

From Bench to Bedside: Patient-Oriented Radiopharmaceutical Development in Nuclear Medicine Based on the Example of [89Zr]Zr-PSMA-DFO.

The interdisciplinary possibilities inherent in nuclear medicine offer an opportunity for the patient-centered development of radioactive pharmaceuticals based on specific research questions. This approach provides radiopharmaceutical manufacturers with a robust scientific foundation on which to navigate the regulatory requirements for drug approval laid down by the law. A vivid illustration of this interdisciplinary cooperation has been the development of a Zr-89-labeled PSMA ligand where reliable results have been obtained across various domains, including chemistry, radiochemistry, biochemistry, and preclinical research. This comprehensive process extended to feasibility studies conducted with carefully selected patients from a single nuclear medicine clinic. The approach demonstrates how far close collaboration between different disciplines within nuclear medicine can further the move towards patient-oriented radiopharmaceutical treatments while simultaneously meeting regulatory demands. With such a strategy, innovative radiopharmaceutical solutions can be brought to the market more swiftly and efficiently, in line with the needs of patients.