First-in-Human Study of 68Ga-FAP-75 PET Imaging of Cancer-associated Fibroblasts

Purpose: Fibroblast activation protein (FAP)-targeted radiopharmaceuticals show promise in cancer imaging, but optimization and development of new radiopharmaceuticals to enhance tumor targeting, prolong retention, and improve diagnostic/therapeutic outcomes are ongoing. This study aims to evaluate the biodistribution, pharmacokinetics, dosimetry, and safety of a novel FAP-targeted probe 68 Ga-FAP-75 in humans, and to preliminarily assess its ability to detect malignant tumors. Patients and Methods: Eight patients with solid tumors underwent positron emission tomography/computed tomography (PET/CT) scans at multiple time points after intravenous injection of 68 Ga-FAP-75 (0.05–0.1 mCi/kg). Regions of interest (ROIs) were drawn on different tissues. Blood and urine samples were collected for analyzing the biodistribution, pharmacokinetics, and radiation dose. The safety of 68 Ga-FAP-75 and its ability to detect malignant tumors were also evaluated. Results: The biodistribution of 68 Ga-FAP-75 in humans was similar to that of other 68 Ga-labeled FAP-targeted probes, with relatively high physiological uptake in the pancreas and uterus. The probe was mainly excreted through the urinary system, with relatively rapid renal excretion and blood clearance rates. Its blood elimination half-life ( T 1/2 ) was 24.66 minutes. The total effective dose of 68 Ga-FAP-75 in humans was 1.17E−02 mSv/MBq. No serious adverse events were observed. 68 Ga-FAP-75 PET/CT clearly detected primary tumors and metastases in all patients. Various lesions showed high 68 Ga-FAP-75 uptake as early as 10 minutes postinjection. The maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) increased gradually, and stabilized within 60–120 minutes. Both tumor-to-liver ratio (TLR) and tumor-to-blood ratio (TBR) increased continuously, showing a favorable target-to-background ratio. Conclusions: The novel FAP-targeted probe 68 Ga-FAP-75 exhibits favorable biodistribution, pharmacokinetics, and safety, with good tumor specificity and a favorable tumor-to-background ratio, showing great potential in tumor imaging and radionuclide-targeted therapy.