89Zr-pembrolizumab imaging as a non-invasive approach to assess clinical response to PD-1 blockade in cancer.

Abstract

BACKGROUND:

Programmed cell death protein 1 (PD-1) antibody treatment is standard of care for melanoma and non-small-cell lung cancer (NSCLC). Accurately predicting which patients will benefit is currently not possible. Tumor uptake and biodistribution of the PD-1 antibody might play a role. Therefore, we carried out a positron emission tomography (PET) imaging study with zirconium-89 (89Zr)-labeled pembrolizumab before PD-1 antibody treatment.

PATIENTS AND METHODS:

Patients with advanced or metastatic melanoma or NSCLC received 37 MBq (1 mCi) 89Zr-pembrolizumab (∼2.5 mg antibody) intravenously plus 2.5 or 7.5 mg unlabeled pembrolizumab. After that, up to three PET scans were carried out on days 2, 4, and 7. Next, PD-1 antibody treatment was initiated. 89Zr-pembrolizumab tumor uptake was calculated as maximum standardized uptake value (SUVmax) and expressed as geometric mean. Normal organ uptake was calculated as SUVmean and expressed as a mean. Tumor response was assessed according to (i)RECIST v1.1.

RESULTS:

Eighteen patients, 11 with melanoma and 7 with NSCLC, were included. The optimal dose was 5 mg pembrolizumab, and the optimal time point for PET scanning was day 7. The tumor SUVmax did not differ between melanoma and NSCLC (4.9 and 6.5, P = 0.49). Tumor 89Zr-pembrolizumab uptake correlated with tumor response (P trend = 0.014) and progression-free (P = 0.0025) and overall survival (P = 0.026). 89Zr-pembrolizumab uptake at 5 mg was highest in the spleen with a mean SUVmean of 5.8 (standard deviation ±1.8). There was also 89Zr-pembrolizumab uptake in Waldeyer's ring, in normal lymph nodes, and at sites of inflammation.

CONCLUSION:

89Zr-pembrolizumab uptake in tumor lesions correlated with treatment response and patient survival. 89Zr-pembrolizumab also showed uptake in lymphoid tissues and at sites of inflammation.

• Authors: I C Kok, J S Hooiveld, P P van de Donk, D Giesen, E L van der Veen, M N Lub-de Hooge, A H Brouwers, T J N Hiltermann, A J van der Wekken, L B M Hijmering-Kappelle, W Timens, S G Elias, G A P Hospers, H J M Groen, W Uyterlinde, B van der Hiel, J B Haanen, D J A de Groot, M Jalving, E G E de Vries
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 33 Issue 1 Pg. 80-88 (01 2022) ISSN: 1569-8041 [Electronic] England
• PMID: 34736925 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier Ltd.

Chemical References

• Antibodies, Monoclonal, Humanized
• Programmed Cell Death 1 Receptor
• pembrolizumab

Topics

• Antibodies, Monoclonal, Humanized
• Carcinoma, Non-Small-Cell Lung (diagnostic imaging, drug therapy, metabolism)
• Humans
• Lung Neoplasms (diagnostic imaging, drug therapy, metabolism)
• Positron-Emission Tomography (methods)
• Programmed Cell Death 1 Receptor
• Tissue Distribution