89Zr-pembrolizumab imaging as a non-invasive approach to assess clinical response to PD-1 blockade in cancer
Iris C. Kok, J.S. Hooiveld, Pim P. van de Donk, Danique Giesen, Elly L. van der Veen, Marjolijn N. Lub–de Hooge, Adrienne H. Brouwers, T. Jeroen N. Hiltermann, Anthonie J. van der Wekken, Lucie B.M. Hijmering-Kappelle, Wim Timens, Sjoerd G. Elias, Geke A.P. Hospers, Harry J.M. Groen, Wilma Uyterlinde, Bernies van der Hiel, John B.A.G. Haanen, Derk Jan A. de Groot, Mathilde Jalving, Elisabeth G.E. de Vries
Abstract
Background: Programmed cell death protein 1 (PD-1) antibody treatment is standard of care for melanoma and nonsmall-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 ( 89 Zr)-labeled pembrolizumab before PD-1 antibody treatment. Patients and methods: Patients with advanced or metastatic melanoma or NSCLC received 37 MBq (1 mCi) 89 Zrpembrolizumab (w2.5 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. 89 Zrpembrolizumab 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 89 Zr-pembrolizumab uptake correlated with tumor response (P trend 0.014) and progression-free (P 0.0025) and overall survival (P 0.026). 89 Zr-pembrolizumab uptake at 5 mg was highest in the spleen with a mean SUV mean of 5.8 (standard deviation AE1.8). There was also 89 Zr-pembrolizumab uptake in Waldeyer's ring, in normal lymph nodes, and at sites of inflammation. Conclusion: 89 Zr-pembrolizumab uptake in tumor lesions correlated with treatment response and patient survival. 89 Zrpembrolizumab also showed uptake in lymphoid tissues and at sites of inflammation.