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Multi-curie production of gallium-68 on a biomedical cyclotron and automated radiolabelling of PSMA-11 and DOTATATE

BACKGROUND: With increasing clinical demand for gallium-68, commercial germanium-68/gallium-68 ([(68)Ge]Ge/[(68)Ga]Ga) generators are incapable of supplying sufficient amounts of the short-lived daughter isotope. In this study, we demonstrate a high-yield, automated method for producing multi-Curie...

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Autores principales: Thisgaard, Helge, Kumlin, Joel, Langkjær, Niels, Chua, Jansen, Hook, Brian, Jensen, Mikael, Kassaian, Amir, Zeisler, Stefan, Borjian, Sogol, Cross, Michael, Schaffer, Paul, Dam, Johan Hygum
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790954/
https://www.ncbi.nlm.nih.gov/pubmed/33411034
http://dx.doi.org/10.1186/s41181-020-00114-9
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author Thisgaard, Helge
Kumlin, Joel
Langkjær, Niels
Chua, Jansen
Hook, Brian
Jensen, Mikael
Kassaian, Amir
Zeisler, Stefan
Borjian, Sogol
Cross, Michael
Schaffer, Paul
Dam, Johan Hygum
author_facet Thisgaard, Helge
Kumlin, Joel
Langkjær, Niels
Chua, Jansen
Hook, Brian
Jensen, Mikael
Kassaian, Amir
Zeisler, Stefan
Borjian, Sogol
Cross, Michael
Schaffer, Paul
Dam, Johan Hygum
author_sort Thisgaard, Helge
collection PubMed
description BACKGROUND: With increasing clinical demand for gallium-68, commercial germanium-68/gallium-68 ([(68)Ge]Ge/[(68)Ga]Ga) generators are incapable of supplying sufficient amounts of the short-lived daughter isotope. In this study, we demonstrate a high-yield, automated method for producing multi-Curie levels of [(68)Ga]GaCl(3) from solid zinc-68 targets and subsequent labelling to produce clinical-grade [(68)Ga]Ga-PSMA-11 and [(68)Ga]Ga-DOTATATE. RESULTS: Enriched zinc-68 targets were irradiated at up to 80 µA with 13 MeV protons for 120 min; repeatedly producing up to 194 GBq (5.24 Ci) of purified gallium-68 in the form of [(68)Ga]GaCl(3) at the end of purification (EOP) from an expected > 370 GBq (> 10 Ci) at end of bombardment. A fully automated dissolution/separation process was completed in 35 min. Isolated product was analysed according to the Ph. Eur. monograph for accelerator produced [(68)Ga]GaCl(3) and found to comply with all specifications. In every instance, the radiochemical purity exceeded 99.9% and importantly, the radionuclidic purity was sufficient to allow for a shelf-life of up to 7 h based on this metric alone. Fully automated production of up to 72.2 GBq [(68)Ga]Ga-PSMA-11 was performed, providing a product with high radiochemical purity (> 98.2%) and very high apparent molar activities of up to 722 MBq/nmol. Further, manual radiolabelling of up to 3.2 GBq DOTATATE was performed in high yields (> 95%) and with apparent molar activities (9–25 MBq/nmol) sufficient for clinical use. CONCLUSIONS: We have developed a high-yielding, automated method for the production of very high amounts of [(68)Ga]GaCl(3), sufficient to supply proximal radiopharmacies. The reported method led to record-high purified gallium-68 activities (194 GBq at end of purification) and subsequent labelling of PSMA-11 and DOTATATE. The process was highly automated from irradiation through to formulation of the product, and as such comprised a high level of radiation protection. The quality control results obtained for both [(68)Ga]GaCl(3) for radiolabelling and [(68)Ga]Ga-PSMA-11 are promising for clinical use.
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spelling pubmed-77909542021-01-19 Multi-curie production of gallium-68 on a biomedical cyclotron and automated radiolabelling of PSMA-11 and DOTATATE Thisgaard, Helge Kumlin, Joel Langkjær, Niels Chua, Jansen Hook, Brian Jensen, Mikael Kassaian, Amir Zeisler, Stefan Borjian, Sogol Cross, Michael Schaffer, Paul Dam, Johan Hygum EJNMMI Radiopharm Chem Research Article BACKGROUND: With increasing clinical demand for gallium-68, commercial germanium-68/gallium-68 ([(68)Ge]Ge/[(68)Ga]Ga) generators are incapable of supplying sufficient amounts of the short-lived daughter isotope. In this study, we demonstrate a high-yield, automated method for producing multi-Curie levels of [(68)Ga]GaCl(3) from solid zinc-68 targets and subsequent labelling to produce clinical-grade [(68)Ga]Ga-PSMA-11 and [(68)Ga]Ga-DOTATATE. RESULTS: Enriched zinc-68 targets were irradiated at up to 80 µA with 13 MeV protons for 120 min; repeatedly producing up to 194 GBq (5.24 Ci) of purified gallium-68 in the form of [(68)Ga]GaCl(3) at the end of purification (EOP) from an expected > 370 GBq (> 10 Ci) at end of bombardment. A fully automated dissolution/separation process was completed in 35 min. Isolated product was analysed according to the Ph. Eur. monograph for accelerator produced [(68)Ga]GaCl(3) and found to comply with all specifications. In every instance, the radiochemical purity exceeded 99.9% and importantly, the radionuclidic purity was sufficient to allow for a shelf-life of up to 7 h based on this metric alone. Fully automated production of up to 72.2 GBq [(68)Ga]Ga-PSMA-11 was performed, providing a product with high radiochemical purity (> 98.2%) and very high apparent molar activities of up to 722 MBq/nmol. Further, manual radiolabelling of up to 3.2 GBq DOTATATE was performed in high yields (> 95%) and with apparent molar activities (9–25 MBq/nmol) sufficient for clinical use. CONCLUSIONS: We have developed a high-yielding, automated method for the production of very high amounts of [(68)Ga]GaCl(3), sufficient to supply proximal radiopharmacies. The reported method led to record-high purified gallium-68 activities (194 GBq at end of purification) and subsequent labelling of PSMA-11 and DOTATATE. The process was highly automated from irradiation through to formulation of the product, and as such comprised a high level of radiation protection. The quality control results obtained for both [(68)Ga]GaCl(3) for radiolabelling and [(68)Ga]Ga-PSMA-11 are promising for clinical use. Springer International Publishing 2021-01-07 /pmc/articles/PMC7790954/ /pubmed/33411034 http://dx.doi.org/10.1186/s41181-020-00114-9 Text en © The Author(s) 2021 Open AccessThis 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/.
spellingShingle Research Article
Thisgaard, Helge
Kumlin, Joel
Langkjær, Niels
Chua, Jansen
Hook, Brian
Jensen, Mikael
Kassaian, Amir
Zeisler, Stefan
Borjian, Sogol
Cross, Michael
Schaffer, Paul
Dam, Johan Hygum
Multi-curie production of gallium-68 on a biomedical cyclotron and automated radiolabelling of PSMA-11 and DOTATATE
title Multi-curie production of gallium-68 on a biomedical cyclotron and automated radiolabelling of PSMA-11 and DOTATATE
title_full Multi-curie production of gallium-68 on a biomedical cyclotron and automated radiolabelling of PSMA-11 and DOTATATE
title_fullStr Multi-curie production of gallium-68 on a biomedical cyclotron and automated radiolabelling of PSMA-11 and DOTATATE
title_full_unstemmed Multi-curie production of gallium-68 on a biomedical cyclotron and automated radiolabelling of PSMA-11 and DOTATATE
title_short Multi-curie production of gallium-68 on a biomedical cyclotron and automated radiolabelling of PSMA-11 and DOTATATE
title_sort multi-curie production of gallium-68 on a biomedical cyclotron and automated radiolabelling of psma-11 and dotatate
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790954/
https://www.ncbi.nlm.nih.gov/pubmed/33411034
http://dx.doi.org/10.1186/s41181-020-00114-9
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