Annals of oncology : official journal of the European Society for Medical Oncology · 2021
89Zr-pembrolizumab imaging as a non-invasive approach to assess clinical response to PD-1 blockade in cancer.
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Kok I C, Hooiveld J S, van de Donk P P, Giesen D, van der Veen E L, Lub-de Hooge M N, Brouwers A H, Hiltermann T J N, van der Wekken A J, Hijmering-Kappelle L B M, Timens W, Elias S G, Hospers G A P, Groen H J M, Uyterlinde W, van der Hiel B, Haanen J B, de Groot D J A, Jalving M, de Vries E G E
Аннотация
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.
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.