Background: Immune checkpoint inhibitors (ICI) targeting programmed cell death protein-1/ligand-1 (PD-1/PD-L1) have shown activity in R/M squamous cell carcinoma of the head and neck (SCCHN). Positron-emission-tomography (PET) with ⁸⁹Zr-labeled anti-PD-L1 antibodies could aid in predicting response to ICI. We present the dose-finding results of the first-in-human ⁸⁹Zr-durvalumab PD-L1 PET-imaging in patients with SCCHN participating in the ongoing phase II PINCH study (NCT03829007). Methods: Following baseline [¹⁸F]FDG-PET and CT/MRI imaging, patients with incurable R/M SCCHN received 37 MBq ⁸⁹Zr-durvalumab and protein dose 2mg, 10mg or 50mg durvalumab. ⁸⁹Zr-durvalumab PD-L1 PET-scan was acquired day 5 post-injection. Plasma pharmacokinetic analyses were performed at day 0 and 5. Standardized uptake values (SUV, mean ± SD) were measured in [¹⁸F]FDG-positive tumor lesion, liver, spleen, bone marrow and bloodpool. PD-L1-expression was assessed on archival tumor tissue using the Ventana PD-L1 (SP263) assay. Results: 14 patients were enrolled and no adverse events were reported. High tracer-retention was observed in liver and spleen, most prominent in patients receiving 2 or 10mg durvalumab. ⁸⁹Zr-durvalumab accumulation within tumors and between patients was heterogeneous and not all [¹⁸F]FDG-positive lesions showed ⁸⁹Zr-durvalumab uptake. Tumor lesions were visualized best using 10 or 50mg durvalumab (SUV_peak 2mg: 3.86 ± 0.79, 10mg: 7.46 ± 2.18, 50mg: 5.57 ± 1.74). Tumor-to-blood-ratios for 10mg durvalumab were highest (2mg: 2.27 ± 0.33, 10mg: 3.44 ± 0.76, 50mg: 1.73 ± 0.99; p = 0.019). PK-analyses confirmed visual prolonged tracer-retention in bloodpool with increasing protein dose. PD-L1-expression was equally distributed amongst dose-groups. Conclusions: This is the first study to show feasibility of ⁸⁹Zr-durvalumab PD-L1 PET in SCCHN patients, demonstrating the highest tumor-to-blood radio with a total dose of 10mg durvalumab. So far, no correlation of tumor PD-L1 expression with ⁸⁹Zr-durvalumab-uptake and PD-L1 expression on archival tissue was found. Next step will be to correlate ⁸⁹Zr-durvalumab PD-L1 PET tumor uptake with durvalumab treatment response in the phase 2 part of the PINCH study. Clinical trial information: NCT03829007.