Safety, dosimetry and preliminary imaging findings of [68Ga]Ga-OncoFAP – a prospective multicenter Phase I clinical trial

Background: Fibroblast Activation Protein (FAP) has emerged as a pan-tumoral target for diagnostic and therapeutic radiopharmaceuticals. Gallium-68-labelled OncoFAP ([68Ga]Ga-OncoFAP), a small organic radioligand with high affinity for human FAP, has shown promising properties in preclinical experiments. In this prospective Phase I study we aimed to assess the safety, the dosimetry, pharmacokinetics, and preliminary imaging findings of [68Ga]Ga-OncoFAP. Methods: In this multicenter Phase I clinical trial (NCT05784597), patients with breast, esophageal, pancreatic, or colorectal cancer were eligible. After a single administration of 250 (225–275) MBq [68Ga]Ga-OncoFAP, we acquired three sets of PET/CT scans (0–30, 60, and 120 min) using 68Ga EARL-accredited scanners. We collected blood and urine samples up to 120 min post injection. Safety was assessed up to 1 week post scan. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v.5. Dosimetry was evaluated centrally. Pharmacokinetics was evaluated based on serial blood samples. Uptake in lesions and healthy organs was evaluated visually and by SUVmax, SUVmean, and tumour:organ ratio. Approval from competent authorities and ethics committees was obtained prior to study start. Results: A total of 18 patients were enrolled. No adverse events related to [68Ga]Ga-OncoFAP were recorded. The whole-body effective dose was 16.6–24.6 mSv/GBq (mean 19.9 mSv/GBq, median 19.4 mSv/GBq). The elimination of [68Ga]Ga-OncoFAP is predominantly kidney-mediated. All patients showed selective tumor uptake within <10 min after administration (SUVmax tumor lesions shortly after injection range 1.99–31.36), which remained stable up to 120 min post injection (SUVmax tumor lesions range 5.04–21.7). Conclusions: [68Ga]Ga-OncoFAP was safe and well tolerated. The dosimetry profile is in line with other clinically used radiopharmaceuticals. [68Ga]Ga-OncoFAP showed optimal pharmacokinetics with rapid blood clearance and renal excretion. [68Ga]Ga-OncoFAP demonstrated promising in PET imaging of a range of solid tumors, providing the rationale for further studies to elucidate its full application.