Fully Automated 89 Zr Labeling and Purification of Antibodies.

Autor:	Poot AJ; Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands., Adamzek KWA; Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands., Windhorst AD; Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands., Vosjan MJWD; BV Cyclotron VU, Amsterdam, The Netherlands., Kropf S; Scintomics GmbH, Fuerstenfeldbruck, Germany; and., Wester HJ; Scintomics GmbH, Fuerstenfeldbruck, Germany; and.; Pharmaceutical Radiochemistry, Technische Universität München, Garching, Germany., van Dongen GAMS; Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands., Vugts DJ; Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands d.vugts@vumc.nl.
Jazyk:	angličtina
Zdroj:	Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2019 May; Vol. 60 (5), pp. 691-695. Date of Electronic Publication: 2018 Dec 07.
DOI:	10.2967/jnumed.118.217158
Abstrakt:	Dozens of monoclonal antibodies (mAbs) have been approved for clinical use, and hundreds more are under development. To support these developments and facilitate a personalized medicine approach, PET imaging and quantification of mAbs, after chelation with desferrioxamine B (DFO) and radiolabeling with 89 Zr, has become attractive. Also, the use of 89 Zr-mAbs in preclinical and clinical studies is expanding rapidly. Despite these rapid developments, 89 Zr radiolabeling is still performed manually. Therefore, we aimed to develop a simple, fully automated, good-manufacturing-practice (GMP)-compliant production procedure for the 89 Zr labeling of mAbs. Such procedures should increase the robustness and capacity of 89 Zr-mAb production while minimizing the radiation dose to the operator. Here, the procedures for fully automated 89 Zr-mAb production are described and applied to produce batches of 89 Zr-DFO- N -suc-cetuximab and 89 Zr-DFO- N -suc-rituximab suitable for clinical use. Both products had to meet the GMP-compliant quality standards with respect to yield, radiochemical purity, protein integrity, antigen binding, sterility, and endotoxin levels. Methods: Automated 89 Zr labeling of mAbs was developed on a Scintomics GRP 2V module and comprised the following steps: reagent transfer to the 89 Zr-containing reaction vial, mixing of the reagents followed by a 60-min reaction at room temperature to obtain optimal radiolabeling yields, and product purification using a PD-10 desalting column. Results: Radiochemical yields of 89 Zr-DFO- N -suc-cetuximab and 89 Zr-DFO- N -suc-rituximab were all more than 90% according to instant thin-layer chromatography. Isolated yields were 74.6% ± 2.0% and 62.6% ± 3.0% for 89 Zr-DFO- N -suc-cetuximab and 89 Zr-DFO- N -suc-rituximab, respectively, which are similar to isolated yields obtained using GMP protocols for manual 89 Zr labeling of mAbs. To meet the GMP-compliant quality standards, only the radiochemically pure fractions were collected from PD-10, resulting in a lower isolated yield than the radiochemical yield according to instant thin-layer chromatography. The radiochemical purity and protein integrity were more than 95% for both products, and the antigen binding was 95.6% ± 0.6% and 87.1% ± 2.2% for 89 Zr-DFO- N -suc-cetuximab and 89 Zr-DFO- N -suc-rituximab, respectively. The products were sterile, and the endotoxin levels were within acceptable limits, allowing future clinical production using this procedure. Conclusion: Procedures for fully automated GMP-compliant production of 89 Zr-mAbs were developed on a commercially available synthesis module, which also allows the GMP production of other radiolabeled mAbs. (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)
Databáze:	MEDLINE
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