39 Lesion detection by [89Zr]Zr-DFO-girentuximab and [18F]FDG PET/CT in mccRCC patients Conjugation, radiolabeling and quality control of [89Zr]Zr-DFO-girentuximab [89Zr]Zr-DFO-girentuximab was produced under good manufacturing practice (GMP) requirements with ≥95% radiochemical purity. To allow for 89Zr-labeling, Girentuximab (Wilex AG, Munich, Germany) was conjugated with the chelator N-succinyldesferrioxamine-B-tetrafluorphenol (N-SucDf-TFP) (obtained from Amsterdam UMC, the Netherlands). Previously, the 89Zr-labeling of girentuximab has only been described for preclinical studies28. After conjugation the intermediate girentuximab-desferal was purified using gel permeation columns (PD10, GE Healthcare Life sciences, Eindhoven, the Netherlands). After dilution to a concentration of 2 mg/ml it was filtered through 0.2 μm Millex GV filter and dispensed. Radiolabeling of DFO-girentuximab with 89Zr was performed under GMP conditions at Radboudumc and transported to participating centers. The final formulation of the radiolabeled product contains a total concentration of girentuximab ([89Zr]Zr-DFO-girentuximab + unlabeled girentuximab) of 5 mg/10 ml. The unlabeled antibody is added to prevent possible hepatic uptake of the radiolabeled monoclonal antibody. The final product contains 37 MBq [89Zr]Zr-DFOgirentuximab at the time of injection. The radiochemical purity (thin layer chromatography, high performance liquid chromatography) was ≥ 95%, while immunoreactive fraction as assessed by a cell binding assay exceeded 80%. Table 1. Lesion detection per imaging modality and per organ. Detection rates (95%CI) Group CT only [18F]FDG-PET/CT and CT [89Zr]-DFO-girentuximab-PET/CT and CT Overall 0.56 (0.50-0.62) 0.84 (0.79-0.88)* 0.91 (0.87-0.94)* According to location Lung 0.62 (0.53-0.71) 0.84 (0.76-0.89)* 0.95 (0.91-0.98)* Lymph node 0.58 (0.46-0.69) 0.94 (0.88-0.97)* 0.83 (0.73-0.89)* Bone 0.16 (0.08-0.32) 0.81 (0.62-0.92)* 0.81 (0.62-0.92)* Soft tissue 0.45 (0.27-0.63) 0.71 (0.51-0.85)* 0.93 (0.78-0.98)* Adrenal gland 0.85 (0.65-0.95) 0.96 (0.77-1.00) 0.93 (0.74-0.98) Kidney 0.70 (0.46-0.87) 0.68 (0.43-0.86) 1.00 (unidentifiable)* Pancreas 0.85 (0.59-0.96) 0.83 (0.55-0.95) 1.00 (unidentifiable)* Concordant pairs were lesions that were visualized on all 3 modalities. 9 PET detected lesions were outside the field of view of CT. *p < 0.001 compared to CT only. 2
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