RT Journal Article SR Electronic T1 First-in-human study of 89Zr-pembrolizumab PET/CT in patients with advanced stage non-small-cell lung cancer JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP jnumed.121.261926 DO 10.2967/jnumed.121.261926 A1 Anna-Larissa Nadia Niemeijer A1 Daniela E Oprea Lager A1 Marc C Huisman A1 Otto S Hoekstra A1 Ronald Boellaard A1 Berlinda van de Veen A1 Idris Bahce A1 Danielle J Vugts A1 Guus AMS van Dongen A1 Erik Thunnissen A1 Egbert Smit A1 Adrianus J. de Langen YR 2021 UL http://jnm.snmjournals.org/content/early/2021/07/22/jnumed.121.261926.abstract AB 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.