Positron Emission Tomography Imaging of Programmed Death 1 Expression in Cancer Patients Using 124I-Labeled Toripalimab A Pilot Clinical Translation Study

Purpose Although anti-programmed cell death molecule-1 (PD-1)/PD-1 ligand therapy has achieved remarkable success in oncology field, the low response rate and lack of accurate prognostic biomarker identifying benefiting patients remain unresolved challenges. This study developed a PD-1 targeting radiotracer I-124-labeled toripalimab (I-124-JS001) for clinical PET imaging and evaluated its biodistribution, safety, and dosimetry in human. Methods Patients with melanoma or urologic cancer confirmed by pathology were enrolled. I-124-JS001 PET/CT and PET/MR were performed with or without coinjection of 5 mg unlabeled JS001, and F-18-FDG PET was undertaken within 1 week. Results Eight melanoma and 3 urologic cancer patients were enrolled. No adverse events were noticed during the whole examination after the injection of I-124-JS001 and an acceptable dosimetry of 0.236 mSv/MBq was found. I-124-JS001 PET/CT showed high uptake in spleen and liver and slight uptake in bone marrow and lung. All primary and metastatic tumor lesions in 11 patients demonstrated different levels of uptake of I-124-JS001 with SUVmax ranging from 0.2 to 4.7. With coinjection of unlabeled JS001, the uptake in spleen was reduced significantly (P < 0.05), whereas tumor uptake and tumor background ratio increased significantly (P < 0.05). Four patients undertook regional I-124-JS001 PET/MR. All tumor lesions were detected effectively with abnormal MR signal on PET/MR, whereas PET/MR detected liver lesions more sensitively than PET/CT. Conclusions The first-in-human study demonstrated I-124-JS001 was a safe tracer for PET with acceptable dosimetry, and the PET/CT results showed a favorable biodistribution. PET/MR could detect liver lesions more sensitively than PET/CT.