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Published in: Nuclear Medicine and Molecular Imaging 2/2021

01-04-2021 | Scintigraphy | Original Article

High-Efficiency Cationic Labeling Algorithm of Macroaggregated Albumin with 68Gallium

Authors: Uğur Ayşe, Gültekin Aziz, Yüksel Doğangün

Published in: Nuclear Medicine and Molecular Imaging | Issue 2/2021

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Abstract

Purpose

The generator product radionuclide gallium-68(68Ga) is widely used for PET/CT imaging agents and the 68Ga-labeled MAA is an attractive alternative to 99mTc-labeled MAA. Using a commercially available MAA labeling kit for 99mTc, we presented a reliable synthesis protocol with a highly efficient, organic solvent-free cationic method in GMP conditions in the Scintomics automated synthesis unit.

Methods

The labeling process was performed by incubating for 7 min at 90 °C in the borax vial containing the generator product 68GaCl3 MAA-HEPES eluted from the PSH+ cartridge with 1.5 mL 5 molar NaCl. Quality control of the final product content was examined, and radiopharmaceutical production was carried out in accordance with GMP guidelines.

Results

68Ga eluted from the generator was obtained in more than 99% radiochemical purity and efficiency. In this case, the labeling efficiency was found to be >99%. When the results of SEM-EDX analysis in the final product were examined, it was determined that most of toxic metals were no appreciable in the product content.

Conclusions

The radiochemical and chemical purity of the final product allows direct use without purification steps to remove “free 68Ga” or other toxic compounds.
Literature
1.
go back to reference Vermeulen K, Vandamme M, Bormans G, Cleeren F. Design and challenges of radiopharmaceuticals. Semin Nucl Med. 2019;49:339–56.CrossRef Vermeulen K, Vandamme M, Bormans G, Cleeren F. Design and challenges of radiopharmaceuticals. Semin Nucl Med. 2019;49:339–56.CrossRef
2.
go back to reference Kumar V, Boddeti DK. (68)Ga-radiopharmaceuticals for PET imaging of infection and inflammation. Recent Results Cancer Res. 2013;194:189–219.CrossRef Kumar V, Boddeti DK. (68)Ga-radiopharmaceuticals for PET imaging of infection and inflammation. Recent Results Cancer Res. 2013;194:189–219.CrossRef
3.
go back to reference Meyer GJ, Mäcke H, Schuhmacher J, Knapp WH, Hofmann M. 68Ga-labelled DOTA-derivatised peptide ligands. Eur J Nucl Med Mol Imaging. 2004;31:1097–104.CrossRef Meyer GJ, Mäcke H, Schuhmacher J, Knapp WH, Hofmann M. 68Ga-labelled DOTA-derivatised peptide ligands. Eur J Nucl Med Mol Imaging. 2004;31:1097–104.CrossRef
4.
go back to reference Eppard E, Homann T, de la Fuente A, Essler M, Rösch F. Optimization of labeling PSMAHBED with ethanol-postprocessed 68Ga and its quality control systems. J Nucl Med. 2017;58:432–7.CrossRef Eppard E, Homann T, de la Fuente A, Essler M, Rösch F. Optimization of labeling PSMAHBED with ethanol-postprocessed 68Ga and its quality control systems. J Nucl Med. 2017;58:432–7.CrossRef
5.
go back to reference Roesch F. Maturation of a key resource–the Germanium-68/Gallium-68 generator: development and new insights. Curr Radiopharm. 2012;5:202–11.CrossRef Roesch F. Maturation of a key resource–the Germanium-68/Gallium-68 generator: development and new insights. Curr Radiopharm. 2012;5:202–11.CrossRef
6.
go back to reference Chao JC, Hong A, Okey RW, Peters RW. Selection of chelating agents for remediation of radionuclide contaminated soil. Proceedings of the Conference on Hazardous Wastes Research. 1 May, Snowbird, Utah; 1998. p. 142–156 Chao JC, Hong A, Okey RW, Peters RW. Selection of chelating agents for remediation of radionuclide contaminated soil. Proceedings of the Conference on Hazardous Wastes Research. 1 May, Snowbird, Utah; 1998. p. 142–156
7.
go back to reference Fernández-Barahona I, Muñoz-Hernando M, Pellico J, Ruiz-Cabello J, Herranz F. Molecular imaging with 68Ga radio-nanomaterials: shedding light on nanoparticles. Appl Sci. 2018;8(7):1098.CrossRef Fernández-Barahona I, Muñoz-Hernando M, Pellico J, Ruiz-Cabello J, Herranz F. Molecular imaging with 68Ga radio-nanomaterials: shedding light on nanoparticles. Appl Sci. 2018;8(7):1098.CrossRef
8.
go back to reference Even GA, Green MA. Gallium-68-labeled macroaggregated human serum albumin, 68Ga-MAA. Nucl Med Biol. 1989;16:319–21. Even GA, Green MA. Gallium-68-labeled macroaggregated human serum albumin, 68Ga-MAA. Nucl Med Biol. 1989;16:319–21.
9.
go back to reference Maziere B, Loc’h C, Steinling M, Comar D. Stable labeling of serum albumin microspheres with gallium-68. Appl Radiat Isot. 1986;37(4):360–1.CrossRef Maziere B, Loc’h C, Steinling M, Comar D. Stable labeling of serum albumin microspheres with gallium-68. Appl Radiat Isot. 1986;37(4):360–1.CrossRef
10.
go back to reference Amor-Coarasa A, Milera A, Carvajal D, Gulec S, McGoron AJ. Lyophilized kit for the preparation of the PET perfusion agent [68Ga]-MAA. Int J Mol Imaging. 2014;7:269365. Amor-Coarasa A, Milera A, Carvajal D, Gulec S, McGoron AJ. Lyophilized kit for the preparation of the PET perfusion agent [68Ga]-MAA. Int J Mol Imaging. 2014;7:269365.
11.
go back to reference Jain A, Subramanian S, Pandey U, Sarma HD, Ram R, Dash A. In-house preparation of macroaggregated albumin (MAA) for 68Ga labeling and its comparison with commercially available MAA. J Radioanal Nucl Chem. 2016;308:817–24.CrossRef Jain A, Subramanian S, Pandey U, Sarma HD, Ram R, Dash A. In-house preparation of macroaggregated albumin (MAA) for 68Ga labeling and its comparison with commercially available MAA. J Radioanal Nucl Chem. 2016;308:817–24.CrossRef
12.
go back to reference Mueller D, Breeman WAP, Klette I, Gottschaldt M, Odparlik A, Baehre M, et al. Radiolabeling of DOTA-like conjugated peptides with generator-produced 68Ga and using NaCl-based cationic elution method. Nat Protoc. 2016;11:1057–66.CrossRef Mueller D, Breeman WAP, Klette I, Gottschaldt M, Odparlik A, Baehre M, et al. Radiolabeling of DOTA-like conjugated peptides with generator-produced 68Ga and using NaCl-based cationic elution method. Nat Protoc. 2016;11:1057–66.CrossRef
13.
go back to reference European Pharmacopoeia Commission, Council of Europe. European pharmacopoeia. 8th ed. Strasbourg: European Directorate for the Quality of Medicines & Health Care, 2013. European Pharmacopoeia Commission, Council of Europe. European pharmacopoeia. 8th ed. Strasbourg: European Directorate for the Quality of Medicines & Health Care, 2013.
14.
go back to reference Skorupa A, Gierak A. Detection and visualization methods used in thin-layer chromatography. J Chromatogr Sci. 2011;24(4):274–80. Skorupa A, Gierak A. Detection and visualization methods used in thin-layer chromatography. J Chromatogr Sci. 2011;24(4):274–80.
15.
go back to reference Mathias CJ, Green MA. A convenient route to [68Ga]Ga-MAA for use as a particulate PET perfusion tracer. Appl Radiat Isot. 2008;66:1910–2.CrossRef Mathias CJ, Green MA. A convenient route to [68Ga]Ga-MAA for use as a particulate PET perfusion tracer. Appl Radiat Isot. 2008;66:1910–2.CrossRef
16.
go back to reference Ament S, Maus S, Reber H, Buchholz HG, Bausbacher N, et al. PET lung ventilation/perfusion imaging using 68Ga aerosol (Galligas) and 68Ga-labeled macroaggregated albumin. Recent Results Cancer Res. 2013;194:395–423.CrossRef Ament S, Maus S, Reber H, Buchholz HG, Bausbacher N, et al. PET lung ventilation/perfusion imaging using 68Ga aerosol (Galligas) and 68Ga-labeled macroaggregated albumin. Recent Results Cancer Res. 2013;194:395–423.CrossRef
17.
go back to reference Breeman WAP, de Jong M, de Blois E, et al. Radiolabelling DOTA-peptides with 68Ga. Eur J Nucl Med Mol Imaging. 2005;32:478–85.CrossRef Breeman WAP, de Jong M, de Blois E, et al. Radiolabelling DOTA-peptides with 68Ga. Eur J Nucl Med Mol Imaging. 2005;32:478–85.CrossRef
18.
Metadata
Title
High-Efficiency Cationic Labeling Algorithm of Macroaggregated Albumin with 68Gallium
Authors
Uğur Ayşe
Gültekin Aziz
Yüksel Doğangün
Publication date
01-04-2021
Publisher
Springer Singapore
Keyword
Scintigraphy
Published in
Nuclear Medicine and Molecular Imaging / Issue 2/2021
Print ISSN: 1869-3474
Electronic ISSN: 1869-3482
DOI
https://doi.org/10.1007/s13139-021-00687-6

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