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 124I-labeled toripalimab (124I-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. 124I-JS001 PET/CT and PET/MR were performed with or without coinjection of 5 mg unlabeled JS001, and 18F-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 124I-JS001 and an acceptable dosimetry of 0.236 mSv/MBq was found. 124I-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 124I-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 124I-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 124I-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.