Sarah Verhoeff

90 Chapter 5 Figure 2. Representative examples images of one patient per dose cohort. For each cohort, the [89Zr]Zr-DFO-durvalumab PET/CT (left) and [18F]FDG PET/CT (right) is presented of one patient. Physiological [89Zr]Zr-DFO-durvalumab is visualized in lymphoid organs (e.g., liver (1), spleen (2)). Tumor lesions are identified by arrows. The PK-analysis at day 5 showed lowest [89Zr]Zr-DFO-durvalumab (%ID/g) plasma concentration in the 2mg cohort (Supplementary Figure S4), while highest concentrations were measured in the 50mg cohort (p=0.077). Dose cohort 10mg showed variable plasma concentrations between patients. In the 2mg cohort, tumor lesions could not be visualized properly, and high tracer retention was observed in the liver and the spleen. At higher antibody doses, liver and spleen uptake decreased and tumor uptake increased. Also, increasing antibody dose resulted in visually prolonged [89Zr]Zr-DFO-durvalumab circulation time. Quantitative analyses showed that mean TTB ratio was highest in the 10mg cohort and lowest in cohort 50mg (cohort 2mg: 2.28±0.61, cohort 10mg: 3.75±0.93, cohort 50mg: 1.48±1.64; p=0.019, Supplementary Figure S5). Based upon the highest TTB ratios, and tumor visualization, we selected 10mg for subsequent [89Zr]Zr-DFO-durvalumab PET imaging.