Development of a SnO2-based 44Ti/44Sc generator for medical applications

Schmidt, Christine E.; Groveman, Sam; Sanders, Vanessa A.; Cutler, Cathy S.; Shusterman, Jennifer A.; Deri, Melissa A.

doi:10.1016/j.chroma.2024.465245

Development of a SnO₂-based ⁴⁴Ti/⁴⁴Sc generator for medical applications

Journal Article · Thu Aug 08 00:00:00 EDT 2024 · Journal of Chromatography

DOI:https://doi.org/10.1016/j.chroma.2024.465245· OSTI ID:2448356

Schmidt, Christine E. ^[1]; Groveman, Sam ^[1]; ^[2]; Cutler, Cathy S. ^[2]; Shusterman, Jennifer A. ^[3]; ^[1]

City Univ. of New York (CUNY), NY (United States)
Brookhaven National Laboratory (BNL), Upton, NY (United States)
City Univ. of New York (CUNY), NY (United States); Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Towards application of ⁴⁴Sc for diagnostic nuclear medicine, a ⁴⁴Ti/⁴⁴Sc generator based on an inorganic resin has been evaluated. Unlike other radionuclide generators used for medical applications, the long-term retention of the parent ⁴⁴Ti is vital due to its long half life. In this work, tin dioxide (SnO₂), a robust inorganic-based resin, has been synthesized and used as the stationary phase for a ⁴⁴Ti/⁴⁴Sc generator. The sorption behavior of ⁴⁴Ti/⁴⁴Sc was tested on SnO₂ with varying acids, concentrations, and times. Preliminary batch study results showed >88 % ⁴⁴Ti retention to the resin at lower acid concentrations (0.05 M HNO₃ and 0.05 M HCl). A pilot generator was evaluated for a year, demonstrating 85.3 ± 2.8 % ⁴⁴Sc elution yields and 0.71 ± 0.14 % ⁴⁴Ti breakthrough in 5 M HNO₃. Based on capacity studies, a 7.4 MBq (200 µCi) upscaled generator system was constructed for further evaluation of the SnO₂ resin stability and the efficacy of the eluted ⁴⁴Sc for radiolabeling. ⁴⁴Sc could be regularly eluted from this generator in 5 M HNO₃ with an overall average radiochemical yield 84.7 ± 9.5 %. Post-elution processing of the ⁴⁴Sc with DGA-normal resin removed all ⁴⁴Ti present and allowed for high ⁴⁴Sc-DOTA labeling yields of 94.2 ± 0.5 %. Overall, SnO₂ has been shown to be a viable material for a ⁴⁴Ti/⁴⁴Sc generator.

View Accepted Manuscript (DOE)

Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States); Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Office of Isotope R&D and Production (IRP)

Grant/Contract Number:: SC0012704; SC0022550; SC0023683; AC52-07NA27344

OSTI ID:: 2448356

Alternate ID(s):: OSTI ID: 2429763
OSTI ID: 2449711

Report Number(s):: BNL--226134-2024-JAAM

Journal Information:: Journal of Chromatography, Journal Name: Journal of Chromatography Vol. 1732; ISSN 0021-9673

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

References (35)

Evaluation of two extraction chromatography resins for scandium and titanium separation for medical isotope production McLain, Derek R.; Brossard, Thomas W.; De Kruijff, Robin Journal of Radioanalytical and Nuclear Chemistry, Vol. 332, Issue 3 https://doi.org/10.1007/s10967-023-08783-x	journal	February 2023
Reduction of tiIV species in aqueous sulfuric and hydrochloric acids i. Titanium speciation Cservenyák, I.; Kelsall, G. H.; Wang, W. Electrochimica Acta, Vol. 41, Issue 4 https://doi.org/10.1016/0013-4686(95)00343-6	journal	March 1996
A scandium generator Greene, Margaret W.; Hillman, Manny The International Journal of Applied Radiation and Isotopes, Vol. 18, Issue 7 https://doi.org/10.1016/0020-708X(67)90121-4	journal	July 1967
Sorption isotherms: A review on physical bases, modeling and measurement Limousin, G.; Gaudet, J. -P.; Charlet, L. Applied Geochemistry, Vol. 22, Issue 2 https://doi.org/10.1016/j.apgeochem.2006.09.010	journal	February 2007
Post-elution processing of 44Ti/44Sc generator-derived 44Sc for clinical application Pruszyński, M.; Loktionova, N. S.; Filosofov, D. V. Applied Radiation and Isotopes, Vol. 68, Issue 9 https://doi.org/10.1016/j.apradiso.2010.04.003	journal	September 2010
Characteristics of SnO2-based 68Ge/68Ga generator and aspects of radiolabelling DOTA-peptides de Blois, Erik; Sze Chan, Ho; Naidoo, Clive Applied Radiation and Isotopes, Vol. 69, Issue 2 https://doi.org/10.1016/j.apradiso.2010.11.015	journal	February 2011
Cyclotron produced 44gSc from natural calcium Severin, G. W.; Engle, J. W.; Valdovinos, H. F. Applied Radiation and Isotopes, Vol. 70, Issue 8 https://doi.org/10.1016/j.apradiso.2012.04.030	journal	August 2012
Preparation and evaluation of SnO2-based 68Ge/68Ga generator made from 68Ge produced through natZn(α,xn) reaction Saha Das, Sujata; Chattopadhyay, Sankha; Alam, Md. Nayer Applied Radiation and Isotopes, Vol. 79 https://doi.org/10.1016/j.apradiso.2013.04.019	journal	September 2013
Inorganic oxides with potential application in the preparation of a 68 Ge/ 68 Ga generator system Romero, E.; Morcillo, M. A. Applied Radiation and Isotopes, Vol. 119 https://doi.org/10.1016/j.apradiso.2016.10.014	journal	January 2017
Evaluation of hydroxamate-based resins towards a more clinically viable 44Ti/44Sc radionuclide generator Gajecki, Leah; Marino, Celine M.; Cutler, Cathy S. Applied Radiation and Isotopes, Vol. 192 https://doi.org/10.1016/j.apradiso.2022.110588	journal	February 2023
Separation of 44Ti from proton irradiated scandium by using solid-phase extraction chromatography and design of 44Ti/44Sc generator system Radchenko, V.; Meyer, C. A. L.; Engle, J. W. Journal of Chromatography A, Vol. 1477 https://doi.org/10.1016/j.chroma.2016.11.047	journal	December 2016
A combined inorganic-organic titanium-44/scandium-44g radiochemical generator Klouda, Jan; Fassbender, Michael E.; Mocko, Veronika Journal of Chromatography A, Vol. 1711 https://doi.org/10.1016/j.chroma.2023.464438	journal	November 2023
Development of a nano-zirconia based 68Ge/68Ga generator for biomedical applications Chakravarty, Rubel; Shukla, Rakesh; Ram, Ramu Nuclear Medicine and Biology, Vol. 38, Issue 4 https://doi.org/10.1016/j.nucmedbio.2010.10.007	journal	May 2011
Cyclotron production of high purity 44m,44 Sc with deuterons from 44 CaCO 3 targets Alliot, C.; Kerdjoudj, R.; Michel, N. Nuclear Medicine and Biology, Vol. 42, Issue 6 https://doi.org/10.1016/j.nucmedbio.2015.03.002	journal	June 2015
Cyclotron production of 44Sc: From bench to bedside van der Meulen, Nicholas P.; Bunka, Maruta; Domnanich, Katharina A. Nuclear Medicine and Biology, Vol. 42, Issue 9 https://doi.org/10.1016/j.nucmedbio.2015.05.005	journal	September 2015
Simultaneous extraction of Ti(IV) and Fe(III) in HCl solution containing multiple metals and the mechanism research Zhu, Keyu; Ren, Xiulian; Li, Huaquan Separation and Purification Technology, Vol. 257 https://doi.org/10.1016/j.seppur.2020.117897	journal	February 2021
Sc-HOPO: A Potential Construct for Use in Radioscandium-Based Radiopharmaceuticals Phipps, Michael D.; Cingoranelli, Shelbie; Bhupathiraju, N. V. S. Dinesh K. Inorganic Chemistry, Vol. 62, Issue 50 https://doi.org/10.1021/acs.inorgchem.2c03931	journal	February 2023
De Novo Approaches to the Solid-Phase Separation of Titanium(IV) and Scandium(III): Translating Speciation Data to Selective On-Bead Chelation toward Applications in Nuclear Medicine Koller, Angus J.; Wang, Lilian; Deluca, Molly Inorganic Chemistry, Vol. 62, Issue 50 https://doi.org/10.1021/acs.inorgchem.3c01493	journal	July 2023
Matching chelators to radiometals for radiopharmaceuticals Price, Eric W.; Orvig, Chris Chem. Soc. Rev., Vol. 43, Issue 1 https://doi.org/10.1039/C3CS60304K	journal	January 2014
Scandium( iii ) complexes of monophosphorus acid DOTA analogues: a thermodynamic and radiolabelling study with ⁴⁴ Sc from cyclotron and from a ⁴⁴ Ti/ ⁴⁴ Sc generator Kerdjoudj, R.; Pniok, M.; Alliot, C. Dalton Transactions, Vol. 45, Issue 4 https://doi.org/10.1039/C5DT04084A	journal	January 2016
New insights for titanium(iv) speciation in acidic media based on UV-visible and ³¹P NMR spectroscopies and molecular modeling Mangold, Lucas; Halleux, Hubert; Leclerc, Sébastien RSC Advances, Vol. 11, Issue 43 https://doi.org/10.1039/D1RA04284J	journal	January 2021
Pseudo-second-order kinetic equations for modeling adsorption systems for removal of ammonium ions using multi-walled carbon nanotube Ersali, S.; Hadadi, V.; Moradi, Omid Fullerenes, Nanotubes and Carbon Nanostructures https://doi.org/10.1080/1536383X.2013.787610	journal	December 2013
Engineering a modular 44Ti/44Sc generator: eluate evaluation in preclinical models and estimation of human radiation dosimetry Benabdallah, Nadia; Zhang, Hanwen; Unnerstall, Ryan EJNMMI Research, Vol. 13, Issue 1 https://doi.org/10.1186/s13550-023-00968-5	journal	February 2023
Image quality analysis of 44Sc on two preclinical PET scanners: a comparison to 68Ga Rosar, Florian; Buchholz, Hans-Georg; Michels, Sebastian EJNMMI Physics, Vol. 7, Issue 1 https://doi.org/10.1186/s40658-020-0286-3	journal	March 2020
Production of scandium radionuclides for theranostic applications: towards standardization of quality requirements Mikolajczak, R.; Huclier-Markai, S.; Alliot, C. EJNMMI Radiopharmacy and Chemistry, Vol. 6, Issue 1 https://doi.org/10.1186/s41181-021-00131-2	journal	May 2021
Die Radionuklidgeneratoren ,¹¹³Sn/^113m In, ⁶⁸Ge/⁶⁸Ga und ⁴⁴Ti/⁴⁴Sc Seidl, E.; Lieser, K. H. ract, Vol. 19, Issue 4 https://doi.org/10.1524/ract.1973.19.4.196	journal	April 1973
A 44Ti/44Sc radionuclide generator for potential application of 44Sc-based PET-radiopharmaceuticals Filosofov, D. V.; Loktionova, N. S.; Rösch, Frank Radiochimica Acta, Vol. 98, Issue 3 https://doi.org/10.1524/ract.2010.1701	journal	January 2010
Cyclotron production of ⁴⁴ Sc for clinical application Krajewski, Seweryn; Cydzik, Izabela; Abbas, Kamel Radiochimica Acta, Vol. 101, Issue 5 https://doi.org/10.1524/ract.2013.2032	journal	May 2013
The Renaissance of the 68Ge/68Ga Radionuclide Generator Initiates New Developments in 68Ga Radiopharmaceutical Chemistry Roesch, Frank; J. Riss, Patrick Current Topics in Medicinal Chemistry, Vol. 10, Issue 16 https://doi.org/10.2174/156802610793176738	journal	November 2010
Promising Prospects for 44Sc-/47Sc-Based Theragnostics: Application of 47Sc for Radionuclide Tumor Therapy in Mice Muller, C.; Bunka, M.; Haller, S. Journal of Nuclear Medicine, Vol. 55, Issue 10 https://doi.org/10.2967/jnumed.114.141614	journal	July 2014
Nano-sized SnO₂ Photocatalysts: Synthesis, Characterization and Their Application for the Degradation of Methylene Blue Dye Uddin, M. T.; Sultana, Y.; Islam, M. A. Journal of Scientific Research, Vol. 8, Issue 3 https://doi.org/10.3329/jsr.v8i3.27524	journal	September 2016
Cyclotron production of 43Sc and 44gSc from enriched 42CaO, 43CaO, and 44CaO targets Becker, Kaelyn V.; Aluicio-Sarduy, Eduardo; Bradshaw, Tyler Frontiers in Chemistry, Vol. 11 https://doi.org/10.3389/fchem.2023.1167783	journal	April 2023
Developments toward the Implementation of 44Sc Production at a Medical Cyclotron van der Meulen, Nicholas P.; Hasler, Roger; Talip, Zeynep Molecules, Vol. 25, Issue 20 https://doi.org/10.3390/molecules25204706	journal	October 2020
Separation of 44Sc from 44Ti in the Context of A Generator System for Radiopharmaceutical Purposes with the Example of [44Sc]Sc-PSMA-617 and [44Sc]Sc-PSMA-I&T Synthesis Larenkov, Anton A.; Makichyan, Artur G.; Iatsenko, Vladimir N. Molecules, Vol. 26, Issue 21 https://doi.org/10.3390/molecules26216371	journal	October 2021
Clinical Translation and First In-Human Use of [ ⁴⁴ Sc]Sc-PSMA-617 for PET Imaging of Metastasized Castrate-Resistant Prostate Cancer Eppard, Elisabeth; de la Fuente, Ana; Benešová, Martina Theranostics, Vol. 7, Issue 18 https://doi.org/10.7150/thno.20586	journal	January 2017

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