Imaging diagnosis and efficacy monitoring by [ 89 Zr]Zr-DFO-KN035 immunoPET in patients with PD-L1-positive solid malignancies

Although programmed death-ligand 1 (PD-L1) inhibitors have achieved efficacy in cancer therapy, their response rate is low. Differences in the prognosis of patients with cancer under anti-PD-L1 treatment are related to the PD-L1 level in tumors. Accurate PD-L1 detection can optimize the accuracy of tumor immunotherapy and avoid ineffective clinical diagnosis and treatments. We investigated the imaging efficiency and therapy monitoring capacity of [ Zr]Zr-DFO-KN035 immunoPET for tumors. We labeled the monodomain anti-PD-L1 antibody KN035 with the radionuclide zirconium-89 and used this tracer for PET imaging. [ Zr]Zr-DFO-KN035 uptakes in patients with PD-L1-positive tumors, including primary and metastatic tumors, as well as in normal tissues, were comparatively assessed by using positron emission tomography/computed tomography imaging. In PD-L1-positive patients, [ Zr]Zr-DFO-KN035 was sensitive in tumor-targeting imaging and could detect multiple metastatic foci, including multiple bone metastases (tumor-to-muscle ratios of 7.102 and 6.118 at 55 and 120 h, respectively) and lymph-node metastases (tumor-to-muscle ratios of 11.346 and 6.542 at 55 and 120 h, respectively). The needed radioactive dose of [ Zr]Zr-DFO-KN035 (55.5-92.5 MBq) used in this study was considerably lower than that of [ F]FDG (370-555 MBq). [ Zr]Zr-DFO-KN035 monitored and predicted the site of adverse reactions in antitumor immunotherapy. Moreover, after antitumor treatment, [ Zr]Zr-DFO-KN035 enabled observational imaging for therapeutic efficacy evaluation, which can help predict patient prognosis. [ Zr]Zr-DFO-KN035 can be used for the diagnosis and therapy monitoring of PD-L1-positive tumors and provide noninvasive and comprehensive observations for tumor diagnostic imaging, prognosis prediction, and efficacy evaluation.