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

J Nucl Med. 2022 Mar;63(3):362-367. doi: 10.2967/jnumed.121.261926. Epub 2021 Jul 16.

Abstract

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 monotherapy 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 ΒΧΡ20 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 = 3) than in patients without a response (n = 9), although this finding 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 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.

Keywords: NSCLC; PET imaging; immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized
  • B7-H1 Antigen / metabolism
  • Carcinoma, Non-Small-Cell Lung* / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Humans
  • Lung Neoplasms* / diagnostic imaging
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / metabolism
  • Positron Emission Tomography Computed Tomography
  • Programmed Cell Death 1 Receptor
  • Tissue Distribution

Substances

  • Antibodies, Monoclonal, Humanized
  • B7-H1 Antigen
  • Programmed Cell Death 1 Receptor
  • pembrolizumab