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

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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

Supplementary Information

The online version contains supplementary material available at 10.1007/s00259-021-05271-w.

Related collections

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The level of administered activity in radionuclide therapy is often limited by haematological toxicity resulting from the absorbed dose delivered to the bone marrow. The purpose of these EANM guidelines is to provide advice to scientists and clinicians on data acquisition and data analysis related to bone-marrow and whole-body dosimetry. The guidelines are divided into sections "Data acquisition" and "Data analysis". The Data acquisition section provides advice on the measurements required for accurate dosimetry including blood samples, quantitative imaging and/or whole-body measurements with a single probe. Issues specific to given radiopharmaceuticals are considered. The Data analysis section provides advice on the calculation of absorbed doses to the whole body and the bone marrow. The total absorbed dose to the bone marrow consists of contributions from activity in the bone marrow itself (self-absorbed dose) and the cross-absorbed dose to the bone marrow from activity in bone, larger organs and the remainder of the body. As radionuclide therapy enters an era where patient-specific dosimetry is used to guide treatments, accurate bone-marrow and whole-body dosimetry will become an essential element of treatment planning. We hope that these guidelines will provide a basis for the optimization and standardization of the treatment of cancer with radiopharmaceuticals, which will facilitate single- and multi-centre radionuclide therapy studies.

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Author and article information

Contributors

Robin I. J. Merkx:

ORCID: http://orcid.org/0000-0002-0846-6775

Robin.Merkx@radboudumc.nl

Journal

Journal ID (nlm-ta): Eur J Nucl Med Mol Imaging

Journal ID (iso-abbrev): Eur J Nucl Med Mol Imaging

Title: European Journal of Nuclear Medicine and Molecular Imaging

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 1619-7070

ISSN (Electronic): 1619-7089

Publication date (Electronic): 2 March 2021

Publication date PMC-release: 2 March 2021

Publication date (Print): 2021

Volume: 48

Issue: 10

Pages: 3277-3285

Affiliations

[1 ]GRID grid.10417.33, ISNI 0000 0004 0444 9382, Department of Medical Imaging: Nuclear Medicine, , Radboudumc, ; Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands

[2 ]GRID grid.10417.33, ISNI 0000 0004 0444 9382, Department of Urology, , Radboudumc, ; Nijmegen, The Netherlands

[3 ]GRID grid.491638.1, ABX-CRO advanced pharmaceutical services, ; Dresden, Germany

Author information

Robin I. J. Merkx http://orcid.org/0000-0002-0846-6775

Article

Publisher ID: 5271

DOI: 10.1007/s00259-021-05271-w

PMC ID: 8426244

PubMed ID: 33651116

SO-VID: 6061f8db-e7bd-462b-9bcb-13153e60046e

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 26 November 2020

Date accepted : 17 February 2021

Custom metadata

ScienceOpen disciplines: Radiology & Imaging

Keywords: organ-based dosimetry,rcc,girentuximab,zirconium-89

Data availability:

ScienceOpen disciplines: Radiology & Imaging

Keywords: organ-based dosimetry, rcc, girentuximab, zirconium-89

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