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by II.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

Annals of Oncology. 2022, 33(1), 80. 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 (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.