First-in-human study of 89Zr-pembrolizumab PET/CT in patients with advanced stage non-small-cell lung cancer

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Background: Tumor programmed-death ligand-1 (PD-L1) proportion score is the current method to select non-small-cell lung cancer (NSCLC) patients for single agent treatment with pembrolizumab, a programmed cell death-1 (PD-1) monoclonal antibody. However, not all patients respond to therapy. Better understanding of in vivo drug behavior may help to select patients that benefit most. Methods: NSCLC patients eligible for pembrolizumab monotherapy as first or later line therapy were enrolled. Patients received two injections of 89Zr-pembrolizumab; one without a preceding dose of pembrolizumab and one with 200 mg pembrolizumab, directly prior to tracer injection. Up to four PET/CT scans were obtained after tracer injection. Post-imaging acquisition, patients were treated with 200 mg pembrolizumab, every three weeks. Tumor uptake and tracer biodistribution were visually assessed and quantified as standardized uptake value (SUV). Tumor tracer uptake was correlated with PD-1 and PD-L1 expression and response to pembrolizumab treatment. Results: Twelve NSCLC patients were included. One patient experienced grade 3 myalgia after tracer injection. 89Zr-pembrolizumab was observed in the blood pool, liver and spleen. Tracer uptake was visualized in 47,2% of 72 tumor lesions measuring ≥20 mm long axis diameter, and substantial uptake heterogeneity was observed within and between patients. Uptake was higher in patients with response to pembrolizumab treatment (n = 3) compared to patients without a response (n = 9), although this was not statistically significant (median SUVpeak 11.4 vs 5.7, P = 0.066). No significant correlations were found with PD-L1 or PD-1 immunohistochemistry. Conclusion: 89Zr-pembrolizumab injection was safe with only one grade 3 adverse event, possibly immune related, out of 12 patients. 89Zr-pembrolizumab tumor uptake was higher in patients with response to pembrolizumab treatment, but did not correlate with PD-L1 or PD-1 immunohistochemistry.

Original languageEnglish
JournalJournal of nuclear medicine : official publication, Society of Nuclear Medicine
Publication statusE-pub ahead of print - 16 Jul 2021

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