Phase I study to assess safety, biodistribution and radiation dosimetry for 89Zr-girentuximab in patients with renal cell carcinoma

Robin I J Merkx, Daphne Lobeek, Mark Konijnenberg, Luis David Jiménez-Franco, Andreas Kluge, Egbert Oosterwijk, Peter F A Mulders, Mark Rijpkema, Robin I J Merkx, Daphne Lobeek, Mark Konijnenberg, Luis David Jiménez-Franco, Andreas Kluge, Egbert Oosterwijk, Peter F A Mulders, Mark Rijpkema

Abstract

Purpose: In this phase I study, we evaluated the safety, biodistribution and dosimetry of [89Zr]Zr-DFO-girentuximab (89Zr-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 89Zr-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: 89Zr-girentuximab was administered in ten patients as per protocol. No treatment-related adverse events ≥ grade 3 were reported. 89Zr-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 89Zr-girentuximab is safe and well tolerated for the administered activities and mass doses and allows quantitative assessment of 89Zr-girentuximab PET/CT imaging in patients with suspicion of ccRCC.

Trial registration: NCT03556046-14th of June, 2018.

Keywords: Girentuximab; Organ-based dosimetry; RCC; Zirconium-89.

Conflict of interest statement

Dr. Andreas Kluge is Chief Medical Advisor at Telix Pharmaceuticals.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
MIP of patient #8 (male 63 years. Mass dose of 10 mg girentuximab) demonstrating a ccRCC tumour in left kidney (red arrow) at 0.5 h p.a. with an increased tumour to background ratio over time. MIP, maximum intensity projection
Fig. 2
Fig. 2
a PET imaging (168 h p.a.; upper row). ceCT (middle row) and fused imaging (lower row) of patient #6 (male 57 years. Mass dose 10 mg girentuximab) showing 89Zr-girentuximab uptake in the adrenal gland (red dotted arrow). Left kidney (red arrowhead) and mediastinal lymph node (red arrow) from left to right. b The MIP of patient #6 at 168 h p.a.; p.a., post-administration; MIP, maximum intensity projection

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