The First in Human Study of ¹²⁴I-JS001 PET/CT & PET/MR Detecting PD-1 Expression In Patients with Melanoma

Purpose: JS001 is a monoclonal antibody against the programmed death-1 (PD-1) receptor. The purpose of this study was to investigate the potent of ¹²⁴I-JS001 PET/CT and PET/MR to assess PD-1 expression in patients with Melanoma and screen the patients that would benefit from JS001 therapy.

Methods: ¹²⁴I-JS001 was produced and quality control was conducted using Radio-TLC. patients with melanoma conformed by pathology were enrolled and underwent the ¹⁸F-FDG PET/CT. Whole body ¹²⁴I-JS001 PET/CT were performed at 2h, 48h, 96h after the injection of ¹²⁴I-JS001. ¹⁸F-FDG or ¹²⁴I-JS001 PET/MR were performed when patients were volunteered. Volumes of interest were drawn on major organs and tumors to evaluate the bio-distribution of the probe and the uptake of tumors.

Results: Four patients with melanoma were enrolled. No adverse events were noticed during the whole examination after the injection of ¹²⁴I-JS001. ¹²⁴I-JS001 PET/CT showed higher uptake in spleen, liver, and blood, and low uptake in the brain, lung and muscle. The biodistribution was similar with that of ⁸⁹Zr-atezolizumab reported before. A female patient with liver metastases showed no significant abnormal uptake in the liver metastases neither on ¹⁸F-FDG PET/CT nor on ¹²⁴I-JS001 PET/CT. Meanwhile ¹⁸F-FDG PET/MR detected the liver metastases with abnormal MR signals effectively. A female patient with plantar melanoma showed high uptake of ¹²⁴I-JS001 in the tumor lesion both on PET/CT and PET/MR. The melanoma lesion in the third patient and the two nodes adjacent to the left parotid gland in the fourth patient who underwent the resection operation of the left conjunctival melanoma showed a little high uptake on ¹⁸F-FDG PET/CT but not on ¹²⁴I-JS001 PET/CT.Conculsion: ¹²⁴I-JS001 was a safe tracer for PET/CT and the PET/CT results showed a favorable biodistribution. ¹²⁴I-JS001 PET/CT and PET/MR can detect tumors with high PD-1 expression. PET/MR could detect liver lesions more sensitively than PET/CT. Key words: Programmed Death-1 Receptor; ¹²⁴I-JS001 PET/CT; PET/MR; Melanoma; Molecular Imaging. Foundation Support: National Natural Science Foundation of China (81671733, 81871386), Beijing Natural Science Foundation(7171002). Ethical Approval: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent was obtained from all patients. The clinical study was approved by the Ethics Committee of the Beijing Cancer Hospital (Ethics Approval License: 2019KT67); The clinical study was registered on Chinese Clinical Trail Registry(ChiCTR1900027666).