Theranostic Radiopharmaceutical-Guided Robotic Surgery for Precision Tumor Resection and Targeted Elimination of Residual Disease in Digestive System Malignancies.

Abstract

BackgroundDigestive system malignancies frequently recur because occult lesions and microscopic residual disease may persist despite apparently complete resection. The authors evaluated an integrated fibroblast activation protein (FAP)-targeted theranostic workflow combining preoperative [68Ga]Ga-FAPI-46 positron emission tomography/computed tomography (PET/CT), intraoperative radiopharmaceutical-guided robotic surgery, and postoperative [177Lu]Lu-FAPI-46 therapy.MethodsIn this prospective translational feasibility study, 36 patients with colorectal (n = 24), gastric (n = 8), or pancreatic (n = 4) adenocarcinoma underwent preoperative [68Ga]Ga-FAPI-46 PET/CT and radiopharmaceutical-guided robotic resection. Patients with postoperative residual disease were considered for [177Lu]Lu-FAPI-46 therapy. Imaging, surgical, pathological, therapeutic, dosimetric, and safety outcomes were assessed.Results[68Ga]Ga-FAPI-46 PET/CT increased lesion detection from 42.6% ± 10.7% to 75.8% ± 11.9% (p = 0.004) and correlated with operative/pathological lesion burden (R2 = 0.7736, p p 177Lu]Lu-FAPI-46. In the treated residual disease subset, residual lesion maximum standardized uptake value and circulating tumor DNA decreased after therapy, with preliminary short-term residual disease control observed in 71% of evaluable cases. Organ-absorbed doses were modest, 9 of 10 treated patients had no grade ≥3 toxicity, and no treatment-limiting safety signal was observed.ConclusionsThis FAP-targeted perioperative theranostic strategy was feasible and showed promising imaging, surgical, therapeutic, and safety performance in digestive system malignancies.