Total-body ¹⁸ F-AlF-RESCA-T4 immuno-PET/CT in patients with solid tumors: Initial experience and potential value in navigating clinical decision-making

Background: Precise selection of patients who may benefit from targeted therapy or immunotherapy is essential in clinical practice. Trophoblast cell surface antigen 2 (Trop2) is an emerging biomarker with theranostic potential. We previously developed single domain antibody (sdAb)-derived tracers specific for Trop2. We translated two of the tracers (i.e., 68 Ga-Ga-NOTA-T4 and 18 F-AlF-RESCA-T4) for clinical use on a traditional short axial field-of-view positron emission tomography/computed tomography (PET/CT) scanner. This study reports the diagnostic performance of 18 F-AlF-RESCA-T4 on a total-body PET/CT scanner and the value in navigating subsequent treatments in patients with solid tumors. Methods: 18 F-AlF-RESCA-T4 was freshly produced on-site and administered to patients recruited into an ongoing investigator-initiated clinical trial. Three patients with solid tumors underwent both low-dose whole-body 18 F-AlF-RESCA-T4 and 18 F-FDG PET/CT scans in two weeks. Immunohistochemistry (IHC) staining was utilized to analyze Trop2 expression in tumors. Results: All lesions were clearly identified by low-dose 18 F-AlF-RESCA-T4 immuno-PET/CT imaging. Region-of-interest (ROI) analysis showed that the kidneys, pancreas, and glands have the highest radiotracer uptake. 18 F-AlF-RESCA-T4 immuno-PET/CT allowed noninvasive visualization of heterogeneous expression of Trop2 in patients with solid tumors, changing the re-staging and clinical decision-making of the patient. Conclusion: Low-dose 18 F-AlF-RESCA-T4 immuno-PET/CT imaging on the total-body PET/CT scanner is feasible. 18 F-AlF-RESCA-T4 can be effectively used to detect primary and metastatic lesions in patients with solid tumors, suggesting the potential for diagnostic and Trop2-based therapeutic applications.