Phase I study to assess safety, biodistribution and radiation dosimetry for 89Zr-girentuximab in patients with renal cell carcinoma
Robin Merkx, Daphne Lobeek, Mark Konijnenberg, Luis David Jiménez‐Franco, Andreas Kluge, Egbert Oosterwijk, Peter F.A. Mulders, Mark Rijpkema
Abstract
Abstract Purpose In this phase I study, we evaluated the safety, biodistribution and dosimetry of [ 89 Zr]Zr-DFO-girentuximab ( 89 Zr-girentuximab) PET/CT imaging in patients with suspicion of clear cell renal cell carcinoma (ccRCC). Methods Ten eligible patients received an intravenous administration of 37 MBq (± 10%) of 89 Zr-girentuximab at mass doses of 5 mg or 10 mg. Safety was evaluated according to the NCI CTCAE (version 4.03). Biodistribution and normal organ dosimetry was performed based on PET/CT images acquired at 0.5, 4, 24, 72 and 168 h post-administration. Additionally, tumour dosimetry was performed in patients with confirmed ccRCC and visible tumour uptake on PET/CT imaging. Results 89 Zr-girentuximab was administered in ten patients as per protocol. No treatment-related adverse events ≥ grade 3 were reported. 89 Zr-girentuximab imaging allowed successful differentiation between ccRCC and non-ccRCC lesions in all patients, as confirmed with histological data. Dosimetry analysis using OLINDA/EXM 2.1 showed that the organs receiving the highest doses (mean ± SD) were the liver (1.86 ± 0.40 mGy/MBq), the kidneys (1.50 ± 0.22 mGy/MBq) and the heart wall (1.45 ± 0.19 mGy/MBq), with a mean whole body effective dose of 0.57 ± 0.08 mSv/MBq. Tumour dosimetry was performed in the 6 patients with histologically confirmed ccRCC resulting in a median tumour-absorbed dose of 4.03 mGy/MBq (range 1.90–11.6 mGy/MBq). Conclusions This study demonstrates that 89 Zr-girentuximab is safe and well tolerated for the administered activities and mass doses and allows quantitative assessment of 89 Zr-girentuximab PET/CT imaging in patients with suspicion of ccRCC. Trial registration NCT03556046—14th of June, 2018