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

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

doi:10.1016/j.annonc.2021.10.213

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

Ann Oncol. 2022 Jan;33(1):80-88. doi: 10.1016/j.annonc.2021.10.213. Epub 2021 Nov 1.

Authors

I C Kok¹, J S Hooiveld¹, P P van de Donk¹, D Giesen¹, E L van der Veen², M N Lub-de Hooge², A H Brouwers³, T J N Hiltermann⁴, A J van der Wekken⁴, L B M Hijmering-Kappelle⁴, W Timens⁵, S G Elias⁶, G A P Hospers¹, H J M Groen⁴, W Uyterlinde⁷, B van der Hiel⁸, J B Haanen⁷, D J A de Groot¹, M Jalving¹, E G E de Vries⁹

Affiliations

¹ Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
² Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
³ Department of Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁴ Department of Pulmonary Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁵ Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁶ Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
⁷ Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
⁸ Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam, The Netherlands.
⁹ Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: e.g.e.de.vries@umcg.nl.

PMID: 34736925
DOI: 10.1016/j.annonc.2021.10.213

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 (SUV_max) and expressed as geometric mean. Normal organ uptake was calculated as SUV_mean 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 SUV_max 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 SUV_mean 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.

Keywords: (89)Zr; PD-1; PET; immunotherapy; pembrolizumab.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal, Humanized
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 / methods
Programmed Cell Death 1 Receptor
Tissue Distribution

Substances

Antibodies, Monoclonal, Humanized
Programmed Cell Death 1 Receptor
pembrolizumab