Sarah Verhoeff

119 [89Zr]Zr-DFO-avelumab PET/CT in early stage NSCLC patients Immunological response Baseline PD-L1 scores as absolute percentages were not associated with improved (pathological) response (Spearman ρ -,15, p = 0.72) [89Zr]Zr-DFO-avelumab PET/CT safety and imaging dose/time-point optimization Seven out of 23 patients (30%) reported infusion-related reactions, including one grade 3 AE. After introducing prophylactic pre-treatment of paracetamol and anti-histaminic, only one low-grade AE was observed. With pre-medication, [89Zr]Zr-DFO-avelumab injection was considered safe. In total, 13 patients were assigned to one of three dose cohorts: 2 mg (n=3), 10 mg (n=6), or 50 mg (n=4) avelumab. The PET/CT data of one patient, 4 days after injection, could not be retrieved due to technical issues. Examples of [89Zr]Zr-DFO-avelumab PET/CT scans per dose cohort are shown in Figure 3. The tracer retention in liver and spleen appears comparable, but the visibility of tumor lesions was better at day 4 compared with day 2. An increasing antibody dose resulted in increased [89Zr]Zr-DFO-avelumab circulation time, with higher concentrations at day 2 compared to day 4. This was supported with PK analyses, showing lowest [89Zr]Zr-DFO-avelumab (%ID/g) plasma concentration in the 2 mg cohort (suppl Figure 2), while the highest concentrations were measured in the 50 mg cohort (ptrend=0.18). As a result, PET-imaging at 4 days after injection was considered better. Figure 3. Representative example images of one patient per dose cohort. A. represents [89Zr]Zr-DFO-avelumab PET/CT 2 days after tracer-injection and B. the [89Zr]ZrDFO-avelumab 4 days after tracer-injection. Physiological [89Zr]Zr-DFO-durvalumab is visualized in lymphoid organs (e.g., liver (1), spleen (2)). Tumor lesions are identified by arrows. Tumor lesions were visualized in all dose cohorts, but 10 mg was considered optimal on visual assessment. In quantitative analyses, the SUVmean in the spleen was higher in the 2 mg cohort (32.5±12.1), compared to 10 mg (13.4±2.0) and 50 mg (6.0±0.5) dose cohort (p=0.009). The highest tumor SUVpeak value was noted in cohort 50mg (tumor uptake 2 mg: 3.3±1.5, 10 mg: 4.6±1.8, 50 mg: 5.5±2.1). Furthermore, mean TTB ratio (of lung lesions) was highest in the 2 mg 6