Positron Emission Tomography Imaging of Programmed Death 1 Expression in Cancer Patients Using 124I-Labeled Toripalimab

Abstract

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.

Positron emission tomography molecular imaging to monitor anti-tumor systemic response for immune checkpoint inhibitor therapy

“…The spleen and liver of the selected patients showed high uptake, and both primary tumors and metastases showed a certain uptake of 124 I-JS001. These results suggest that the 124 I-JS001 probe combined with PET imaging may be an effective tool for clinical screening of PD1-positive patients for tumor immunotherapy [82]. Furthermore, the first-in-human pilot study of 89 Zr-atezolizumab probe application (NCT02453984 and NCT02478099) was conducted in a total of 25 patients with malignancies, including locally advanced or metastatic bladder cancer, NSCLC, or triplenegative breast cancer (TNBC), 22 of whom completed 4 PET scans and received atezolizumab treatment until disease progression (PD).…”

“…This may reflect the function of the PD1/PDL1 checkpoint in inducing peripheral T cell self-tolerance and limiting the induction of effector T cells [79]. The upregulation of extralymphatic tissue under inflammatory conditions suggests that it induces T cell depletion, limiting the activity, survival, and expansion of effector T cells, and protecting peripheral tissues from immune-mediated damages [81,82].…”

Construction and Preclinical Evaluation of a 124/125I-Labeled Specific Antibody Targeting PD-L2 in Lung Cancer

“…The tracer 124 I-ATL2 in this study has a similar molecular weight and metabolic characteristics as 124 I-JS001 mentioned above, but the former is more rapidly distributed in the tumor area and has a higher clearance rate in the model mice. Furthermore, the clinical translation of 124 I-JS001 by our group can also provide experience for the clinical application of the novel PD-L2-targeted tracer in this study …”

“…Furthermore, the clinical translation of 124 I-JS001 by our group can also provide experience for the clinical application of the novel PD-L2-targeted tracer in this study. 24 This study has the following innovations. First, 124/125 I-ATL2 was the first imaging tracer targeting PD-L2, which provides a preliminary reference for subsequent research on this target.…”

“…A volume of 2.5 μL was taken out as a standard. After mice were sacrificed at different time points (1,4,24,48,96, and 120 h), organs were collected and weighed and then measured by a γ-counter. The experimental results were calculated as %ID/g.…”