Study of 89Zr-Pembrolizumab PET/CT in Patients with Advanced-Stage Non-Small Cell Lung Cancer

Anna-Larissa N. Niemeijer, Daniela E. Oprea-Lager, Marc C. Huisman, Otto S. Hoekstra, Ronald Boellaard, Berlinda J. de Wit-van der Veen, Idris Bahce, Danielle J. Vugts, Guus A. M. S. van Dongen, Erik Thunnissen, Egbert F. Smit, Adrianus J. de Langen

Research output: Contribution to journalArticleAcademicpeer-review


The tumor programmed death ligand 1 (PD-L1) proportion score is the current method for selecting 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 in the selection of patients who will benefit the most. Methods: NSCLC patients eligible for pembrolizumab mono-therapy as first- or later-line therapy were enrolled. Patients received 2 injections of 89Zr-pembrolizumab, 1 without a preceding dose of pembrolizumab and 1 with a preceding dose of 200 mg of pembrolizumab, directly before tracer injection. Up to 4 PET/CT scans were obtained after tracer injection. After imaging acquisition, patients were treated with 200 mg of pembrolizumab every 3 wk. Tumor uptake and tracer biodistribution were visually assessed and quantified as the 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 BXP20 mm in the long-axis diameter, and substantial uptake heterogeneity was observed within and between patients. Uptake was higher in patients with a response to pembrolizumab treatment (n 5 3) than in patients without a response (n 5 9), although this finding was not statistically significant (median SUVpeak, 11.4 vs. 5.7; P 5 0.066). No significant correlations were found with PD-L1 or PD-1 immunohistochemistry. Conclusion: 89Zr-pembrolizumab injection was safe, with only 1 grade 3 adverse event-possibly immune-related-in 12 patients. 89Zr-pembrolizumab tumor uptake was higher in patients with a response to pembrolizumab treatment but did not correlate with PD-L1 or PD-1 immunohistochemistry.

Original languageEnglish
Pages (from-to)362-367
Number of pages6
JournalJournal of nuclear medicine : official publication, Society of Nuclear Medicine
Issue number3
Early online date16 Jul 2021
Publication statusPublished - 1 Mar 2022

Cite this