Cyclotron production and radiochemical purification of terbium-155 for SPECT imaging

Abstract Background Terbium-155 [T1/2 = 5.32 d, Eγ = 87 keV (32%) 105 keV (25%)] is an interesting radionuclide suitable for single photon emission computed tomography (SPECT) imaging with potential application in the diagnosis of oncological disease. It shows similar decay characteristics to the cl...

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Autores principales:	C. Favaretto, Z. Talip, F. Borgna, P. V. Grundler, G. Dellepiane, A. Sommerhalder, H. Zhang, R. Schibli, S. Braccini, C. Müller, N. P. van der Meulen
Formato:	article
Lenguaje:	EN
Publicado:	SpringerOpen 2021
Materias:	Terbium-155 Matched pairs Radiolanthanides Theragnostics Radionuclide production Proton irradiation Medical physics. Medical radiology. Nuclear medicine R895-920 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/6ebd72eb03ab44f6b53081c7ebb3a98e
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spelling	oai:doaj.org-article:6ebd72eb03ab44f6b53081c7ebb3a98e2021-11-21T12:26:58ZCyclotron production and radiochemical purification of terbium-155 for SPECT imaging10.1186/s41181-021-00153-w2365-421Xhttps://doaj.org/article/6ebd72eb03ab44f6b53081c7ebb3a98e2021-11-01T00:00:00Zhttps://doi.org/10.1186/s41181-021-00153-whttps://doaj.org/toc/2365-421XAbstract Background Terbium-155 [T1/2 = 5.32 d, Eγ = 87 keV (32%) 105 keV (25%)] is an interesting radionuclide suitable for single photon emission computed tomography (SPECT) imaging with potential application in the diagnosis of oncological disease. It shows similar decay characteristics to the clinically established indium-111 and would be a useful substitute for the diagnosis and prospective dosimetry with biomolecules that are afterwards labeled with therapeutic radiolanthanides and pseudo-radiolanthanides, such as lutetium-177 and yttrium-90. Moreover, terbium-155 could form part of the perfect “matched pair” with the therapeutic radionuclide terbium-161, making the concept of true radiotheragnostics a reality. The aim of this study was the investigation of the production of terbium-155 via the 155Gd(p,n)155Tb and 156Gd(p,2n)155Tb nuclear reactions and its subsequent purification, in order to obtain a final product in quantity and quality sufficient for preclinical application. The 156Gd(p,2n)155Tb nuclear reaction was performed with 72 MeV protons (degraded to ~ 23 MeV), while the 155Gd(p,n)155Tb reaction was degraded further to ~ 10 MeV, as well as performed at an 18 MeV medical cyclotron, to demonstrate its feasibility of production. Result The 156Gd(p,2n)155Tb nuclear reaction demonstrated higher production yields of up to 1.7 GBq, however, lower radionuclidic purity when compared to the final product (~ 200 MBq) of the 155Gd(p,n)155Tb nuclear reaction. In particular, other radioisotopes of terbium were produced as side products. The radiochemical purification of terbium-155 from the target material was developed to provide up to 1.0 GBq product in a small volume (~ 1 mL 0.05 M HCl), suitable for radiolabeling purposes. The high chemical purity of terbium-155 was proven by radiolabeling experiments at molar activities up to 100 MBq/nmol. SPECT/CT experiments were performed in tumor-bearing mice using [155Tb]Tb-DOTATOC. Conclusion This study demonstrated two possible production routes for high activities of terbium-155 using a cyclotron, indicating that the radionuclide is more accessible than the exclusive mass-separated method previously demonstrated. The developed radiochemical purification of terbium-155 from the target material yielded [155Tb]TbCl3 in high chemical purity. As a result, initial cell uptake investigations, as well as SPECT/CT in vivo studies with [155Tb]Tb-DOTATOC, were successfully performed, indicating that the chemical separation produced a product with suitable quality for preclinical studies.C. FavarettoZ. TalipF. BorgnaP. V. GrundlerG. DellepianeA. SommerhalderH. ZhangR. SchibliS. BracciniC. MüllerN. P. van der MeulenSpringerOpenarticleTerbium-155Matched pairsRadiolanthanidesTheragnosticsRadionuclide productionProton irradiationMedical physics. Medical radiology. Nuclear medicineR895-920Therapeutics. PharmacologyRM1-950ENEJNMMI Radiopharmacy and Chemistry, Vol 6, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Terbium-155 Matched pairs Radiolanthanides Theragnostics Radionuclide production Proton irradiation Medical physics. Medical radiology. Nuclear medicine R895-920 Therapeutics. Pharmacology RM1-950
spellingShingle	Terbium-155 Matched pairs Radiolanthanides Theragnostics Radionuclide production Proton irradiation Medical physics. Medical radiology. Nuclear medicine R895-920 Therapeutics. Pharmacology RM1-950 C. Favaretto Z. Talip F. Borgna P. V. Grundler G. Dellepiane A. Sommerhalder H. Zhang R. Schibli S. Braccini C. Müller N. P. van der Meulen Cyclotron production and radiochemical purification of terbium-155 for SPECT imaging
description	Abstract Background Terbium-155 [T1/2 = 5.32 d, Eγ = 87 keV (32%) 105 keV (25%)] is an interesting radionuclide suitable for single photon emission computed tomography (SPECT) imaging with potential application in the diagnosis of oncological disease. It shows similar decay characteristics to the clinically established indium-111 and would be a useful substitute for the diagnosis and prospective dosimetry with biomolecules that are afterwards labeled with therapeutic radiolanthanides and pseudo-radiolanthanides, such as lutetium-177 and yttrium-90. Moreover, terbium-155 could form part of the perfect “matched pair” with the therapeutic radionuclide terbium-161, making the concept of true radiotheragnostics a reality. The aim of this study was the investigation of the production of terbium-155 via the 155Gd(p,n)155Tb and 156Gd(p,2n)155Tb nuclear reactions and its subsequent purification, in order to obtain a final product in quantity and quality sufficient for preclinical application. The 156Gd(p,2n)155Tb nuclear reaction was performed with 72 MeV protons (degraded to ~ 23 MeV), while the 155Gd(p,n)155Tb reaction was degraded further to ~ 10 MeV, as well as performed at an 18 MeV medical cyclotron, to demonstrate its feasibility of production. Result The 156Gd(p,2n)155Tb nuclear reaction demonstrated higher production yields of up to 1.7 GBq, however, lower radionuclidic purity when compared to the final product (~ 200 MBq) of the 155Gd(p,n)155Tb nuclear reaction. In particular, other radioisotopes of terbium were produced as side products. The radiochemical purification of terbium-155 from the target material was developed to provide up to 1.0 GBq product in a small volume (~ 1 mL 0.05 M HCl), suitable for radiolabeling purposes. The high chemical purity of terbium-155 was proven by radiolabeling experiments at molar activities up to 100 MBq/nmol. SPECT/CT experiments were performed in tumor-bearing mice using [155Tb]Tb-DOTATOC. Conclusion This study demonstrated two possible production routes for high activities of terbium-155 using a cyclotron, indicating that the radionuclide is more accessible than the exclusive mass-separated method previously demonstrated. The developed radiochemical purification of terbium-155 from the target material yielded [155Tb]TbCl3 in high chemical purity. As a result, initial cell uptake investigations, as well as SPECT/CT in vivo studies with [155Tb]Tb-DOTATOC, were successfully performed, indicating that the chemical separation produced a product with suitable quality for preclinical studies.
format	article
author	C. Favaretto Z. Talip F. Borgna P. V. Grundler G. Dellepiane A. Sommerhalder H. Zhang R. Schibli S. Braccini C. Müller N. P. van der Meulen
author_facet	C. Favaretto Z. Talip F. Borgna P. V. Grundler G. Dellepiane A. Sommerhalder H. Zhang R. Schibli S. Braccini C. Müller N. P. van der Meulen
author_sort	C. Favaretto
title	Cyclotron production and radiochemical purification of terbium-155 for SPECT imaging
title_short	Cyclotron production and radiochemical purification of terbium-155 for SPECT imaging
title_full	Cyclotron production and radiochemical purification of terbium-155 for SPECT imaging
title_fullStr	Cyclotron production and radiochemical purification of terbium-155 for SPECT imaging
title_full_unstemmed	Cyclotron production and radiochemical purification of terbium-155 for SPECT imaging
title_sort	cyclotron production and radiochemical purification of terbium-155 for spect imaging
publisher	SpringerOpen
publishDate	2021
url	https://doaj.org/article/6ebd72eb03ab44f6b53081c7ebb3a98e
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Cyclotron production and radiochemical purification of terbium-155 for SPECT imaging

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