High Yield Production and Radiochemical Isolation of Isotopically Pure Arsenic-72 and Novel Radioarsenic Labeling Strategies for the Development of Theranostic Radiopharmaceuticals
Abstract
Radioisotopes of arsenic are of considerable interest to the field of nuclear medicine with unique nuclear and chemical properties making them well-suited for use in novel theranostic radiopharmaceuticals. However, progress must still be made in the production of isotopically pure radioarsenic and in its stable conjugation to biological targeting vectors. This work presents the production and irradiation of isotopically enriched 72Ge(m) discs in an irrigation-cooled target system allowing for the production of isotopically pure 72As with capability on the order of 10 GBq. A radiochemical separation procedure isolated the reactive trivalent radioarsenic in a small volume buffered aqueous solution, while reclaiming 72Ge target material. The direct thiol-labeling of a monoclonal antibody resulted in a conjugate exhibiting exceptionally poor in vivo stability in a mouse model. This prompted further investigations to alternative radioarsenic labeling strategies, including the labeling of the dithiol-containing chelator dihydrolipoic acid, and thiol-modified mesoporous silica nanoparticles (MSN-SH). In conclusion, radioarsenic-labeled MSN-SH showed exceptional in vivo stability toward dearsenylation.
- Authors:
-
- Univ. of Wisconsin School of Medicine and Public Health, Madison, WI (United States)
- TRACON Pharmaceuticals, Inc., San Diego, CA (United States)
- Univ. of Wisconsin School of Medicine and Public Health, Madison, WI (United States); Univ. of Wisconsin, Madison, WI (United States)
- Publication Date:
- Research Org.:
- Univ. of Wisconsin, Madison, WI (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1467565
- Grant/Contract Number:
- SC0005281; SC0008384
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Bioconjugate Chemistry
- Additional Journal Information:
- Journal Volume: 27; Journal Issue: 1; Journal ID: ISSN 1043-1802
- Publisher:
- American Chemical Society
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
Citation Formats
Ellison, Paul A., Barnhart, Todd E., Chen, Feng, Hong, Hao, Zhang, Yin, Theuer, Charles P., Cai, Weibo, Nickles, Robert J., and DeJesus, Onofre T. High Yield Production and Radiochemical Isolation of Isotopically Pure Arsenic-72 and Novel Radioarsenic Labeling Strategies for the Development of Theranostic Radiopharmaceuticals. United States: N. p., 2015.
Web. doi:10.1021/acs.bioconjchem.5b00592.
Ellison, Paul A., Barnhart, Todd E., Chen, Feng, Hong, Hao, Zhang, Yin, Theuer, Charles P., Cai, Weibo, Nickles, Robert J., & DeJesus, Onofre T. High Yield Production and Radiochemical Isolation of Isotopically Pure Arsenic-72 and Novel Radioarsenic Labeling Strategies for the Development of Theranostic Radiopharmaceuticals. United States. https://doi.org/10.1021/acs.bioconjchem.5b00592
Ellison, Paul A., Barnhart, Todd E., Chen, Feng, Hong, Hao, Zhang, Yin, Theuer, Charles P., Cai, Weibo, Nickles, Robert J., and DeJesus, Onofre T. Tue .
"High Yield Production and Radiochemical Isolation of Isotopically Pure Arsenic-72 and Novel Radioarsenic Labeling Strategies for the Development of Theranostic Radiopharmaceuticals". United States. https://doi.org/10.1021/acs.bioconjchem.5b00592. https://www.osti.gov/servlets/purl/1467565.
@article{osti_1467565,
title = {High Yield Production and Radiochemical Isolation of Isotopically Pure Arsenic-72 and Novel Radioarsenic Labeling Strategies for the Development of Theranostic Radiopharmaceuticals},
author = {Ellison, Paul A. and Barnhart, Todd E. and Chen, Feng and Hong, Hao and Zhang, Yin and Theuer, Charles P. and Cai, Weibo and Nickles, Robert J. and DeJesus, Onofre T.},
abstractNote = {Radioisotopes of arsenic are of considerable interest to the field of nuclear medicine with unique nuclear and chemical properties making them well-suited for use in novel theranostic radiopharmaceuticals. However, progress must still be made in the production of isotopically pure radioarsenic and in its stable conjugation to biological targeting vectors. This work presents the production and irradiation of isotopically enriched 72Ge(m) discs in an irrigation-cooled target system allowing for the production of isotopically pure 72As with capability on the order of 10 GBq. A radiochemical separation procedure isolated the reactive trivalent radioarsenic in a small volume buffered aqueous solution, while reclaiming 72Ge target material. The direct thiol-labeling of a monoclonal antibody resulted in a conjugate exhibiting exceptionally poor in vivo stability in a mouse model. This prompted further investigations to alternative radioarsenic labeling strategies, including the labeling of the dithiol-containing chelator dihydrolipoic acid, and thiol-modified mesoporous silica nanoparticles (MSN-SH). In conclusion, radioarsenic-labeled MSN-SH showed exceptional in vivo stability toward dearsenylation.},
doi = {10.1021/acs.bioconjchem.5b00592},
journal = {Bioconjugate Chemistry},
number = 1,
volume = 27,
place = {United States},
year = {Tue Dec 08 00:00:00 EST 2015},
month = {Tue Dec 08 00:00:00 EST 2015}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 30 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Theranostics: Combining Imaging and Therapy
journal, October 2011
- Kelkar, Sneha S.; Reineke, Theresa M.
- Bioconjugate Chemistry, Vol. 22, Issue 10
68Gallium- and 90Yttrium-/177Lutetium: “theranostic twins” for diagnosis and treatment of NETs
journal, August 2014
- Werner, Rudolf A.; Bluemel, Christina; Allen-Auerbach, Martin S.
- Annals of Nuclear Medicine, Vol. 29, Issue 1
Radioiodine: The Classic Theranostic Agent
journal, May 2012
- Silberstein, Edward B.
- Seminars in Nuclear Medicine, Vol. 42, Issue 3
Selenium-72 formation via natBr(p,x) induced by 100MeV Protons: Steps towards a novel 72Se/72As generator system
journal, April 2012
- Ballard, B.; Wycoff, D.; Birnbaum, E. R.
- Applied Radiation and Isotopes, Vol. 70, Issue 4
Novel radiochemical separation of arsenic from selenium for 72Se/72As generator
journal, May 2012
- Chajduk, Ewelina; Doner, Katarzyna; Polkowska-Motrenko, Halina
- Applied Radiation and Isotopes, Vol. 70, Issue 5
Separation of no-carrier-added arsenic-77 from neutron irradiated germanium
journal, January 2009
- Bokhari, Tanveer Hussain; Ahmad, Mushtaq; Khan, Islam Ullah
- Radiochimica Acta, Vol. 97, Issue 9
How acute promyelocytic leukaemia revived arsenic
journal, September 2002
- Zhu, Jun; Chen, Zhu; Lallemand-Breitenbach, Valérie
- Nature Reviews Cancer, Vol. 2, Issue 9
Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide
journal, July 2007
- Lu, J.; Chew, E. -H.; Holmgren, A.
- Proceedings of the National Academy of Sciences, Vol. 104, Issue 30
Arsenical-based cancer drugs
journal, October 2007
- Dilda, Pierre J.; Hogg, Philip J.
- Cancer Treatment Reviews, Vol. 33, Issue 6
Anticancer Activity of Small-Molecule and Nanoparticulate Arsenic(III) Complexes
journal, October 2013
- Swindell, Elden P.; Hankins, Patrick L.; Chen, Haimei
- Inorganic Chemistry, Vol. 52, Issue 21
Separation of radioarsenic from a germanium dioxide target
journal, January 1990
- Billinghurst, Mervyn W.; Abrams, Douglas N.; Cantor, Sheila
- International Journal of Radiation Applications and Instrumentation. Part A. Applied Radiation and Isotopes, Vol. 41, Issue 5
Separation of arsenic from germanium oxide targets by dry distillation
journal, January 2001
- Tolmachev, V.; Lundqvist, H.
- Journal of Radioanalytical and Nuclear Chemistry, Vol. 247, Issue 1, p. 61-66
A new method for radiochemical separation of arsenic from irradiated germanium oxide
journal, September 2005
- Jennewein, M.; Qaim, S. M.; Hermanne, A.
- Applied Radiation and Isotopes, Vol. 63, Issue 3, p. 343-351
Separation of radioarsenic from irradiated germanium oxide targets for the production of 71As and 72As
journal, August 2010
- Shehata, M. M.; Scholten, B.; Spahn, I.
- Journal of Radioanalytical and Nuclear Chemistry, Vol. 287, Issue 2
Preparation and Isolation of Carrier‐Free As 74 from Germanium Cyclotron Targets
journal, April 1954
- Green, Mino; Kafalas, James A.
- The Journal of Chemical Physics, Vol. 22, Issue 4
Cyclotron-produced carrier-free radioisotopes
journal, February 1959
- Gruverman, Irwin J.; Kruger, Paul
- The International Journal of Applied Radiation and Isotopes, Vol. 5, Issue 1
Separation of Radioactive Arsenic from Germanium Irradiated with Protons
journal, July 1960
- Saito, Kazuo; Ikeda, Shigerô; Saito, Makoto
- Bulletin of the Chemical Society of Japan, Vol. 33, Issue 7
Separation of carrier-free arsenic from germanium
journal, January 1998
- Guin, R.; Das, S. K.; Saha, S. K.
- Journal of Radioanalytical and Nuclear Chemistry, Vol. 227, Issue 1-2
Separation and purification of no-carrier-added arsenic from bulk amounts of germanium for use in radiopharmaceutical labelling
journal, January 2010
- Jahn, M.; Radchenko, V.; Filosofov, D. V.
- Radiochimica Acta, Vol. 98, Issue 12
Hydrogen Reduction of Germanium Dioxide
journal, January 1972
- Hasegawa, Ryosuke; Kurosawa, Toshio; Yagihashi, Tetsuo
- Transactions of the Japan Institute of Metals, Vol. 13, Issue 1
Anion-exchange Studies. XVIII. Germanium and Arsenic in HCl Solutions 1,2
journal, September 1955
- Nelson, Frederick; Kraus, Kurt A.
- Journal of the American Chemical Society, Vol. 77, Issue 17
Vascular Imaging of Solid Tumors in Rats with a Radioactive Arsenic-Labeled Antibody that Binds Exposed Phosphatidylserine
journal, March 2008
- Jennewein, M.; Lewis, M. A.; Zhao, D.
- Clinical Cancer Research, Vol. 14, Issue 5, p. 1377-1385
A Phase I First-in-Human Study of TRC105 (Anti-Endoglin Antibody) in Patients with Advanced Cancer
journal, July 2012
- Rosen, Lee S.; Hurwitz, Herbert I.; Wong, Michael K.
- Clinical Cancer Research, Vol. 18, Issue 17
An Open-Label Phase Ib Dose-Escalation Study of TRC105 (Anti-Endoglin Antibody) with Bevacizumab in Patients with Advanced Cancer
journal, September 2014
- Gordon, Michael S.; Robert, Francisco; Matei, Daniela
- Clinical Cancer Research, Vol. 20, Issue 23
A phase I study of TRC105 anti-endoglin (CD105) antibody in metastatic castration-resistant prostate cancer: Phase I study of TRC105 in castration-resistant prostate cancer
journal, June 2015
- Karzai, Fatima H.; Apolo, Andrea B.; Cao, Liang
- BJU International, Vol. 116, Issue 4
Positron emission tomography imaging of CD105 expression during tumor angiogenesis
journal, March 2011
- Hong, Hao; Yang, Yunan; Zhang, Yin
- European Journal of Nuclear Medicine and Molecular Imaging, Vol. 38, Issue 7
Positron emission tomography imaging of CD105 expression with 89Zr-Df-TRC105
journal, September 2011
- Hong, Hao; Severin, Gregory W.; Yang, Yunan
- European Journal of Nuclear Medicine and Molecular Imaging, Vol. 39, Issue 1
Experience with the iodine-123 and technetium-99m labelled anti-granulocyte antibody MAb47: a comparison of labelling methods
journal, July 1995
- Bl�uenstein, Peter; Locher, Johannes T.; Seybold, Klaus
- European Journal of Nuclear Medicine, Vol. 22, Issue 7
Arsenic trioxide binding to serum proteins
journal, July 2015
- Shooshtary, Sara; Behtash, Sima; Nafisi, Shohreh
- Journal of Photochemistry and Photobiology B: Biology, Vol. 148
Equilibrium characterization of the As(III)–cysteine and the As(III)–glutathione systems in aqueous solution
journal, June 2004
- Rey, Nicolás A.; Howarth, Oliver W.; Pereira-Maia, Elene C.
- Journal of Inorganic Biochemistry, Vol. 98, Issue 6
Thermodynamics of the As(III)−Thiol Interaction: Arsenite and Monomethylarsenite Complexes with Glutathione, Dihydrolipoic Acid, and Other Thiol Ligands
journal, March 2005
- Spuches, Anne M.; Kruszyna, Harriet G.; Rich, Anne M.
- Inorganic Chemistry, Vol. 44, Issue 8
Click-Chemistry Strategy for Labeling Antibodies with Copper-64 via a Cross-Bridged Tetraazamacrocyclic Chelator Scaffold
journal, March 2015
- Kumar, Amit; Hao, Guiyang; Liu, Li
- Bioconjugate Chemistry, Vol. 26, Issue 4
Matching chelators to radiometals for radiopharmaceuticals
journal, January 2014
- Price, Eric W.; Orvig, Chris
- Chem. Soc. Rev., Vol. 43, Issue 1
Synthesis of tridentate ligand: Potential theranostic application of a radioarsenic trithiol complex
journal, August 2014
- DeGraffenreid, Anthony J.; Cutler, Cathy S.; Barnes, Charles
- Nuclear Medicine and Biology, Vol. 41, Issue 7
Alpha-lipoic acid as a biological antioxidant
journal, August 1995
- Packer, Lester; Witt, Eric H.; Tritschler, Hans Jürgen
- Free Radical Biology and Medicine, Vol. 19, Issue 2
In Vivo Targeting and Imaging of Tumor Vasculature with Radiolabeled, Antibody-Conjugated Nanographene
journal, February 2012
- Hong, Hao; Yang, Kai; Zhang, Yin
- ACS Nano, Vol. 6, Issue 3
72/74As-labeling of HPMA based polymers for long-term in vivo PET imaging
journal, September 2010
- Herth, Matthias M.; Barz, Matthias; Jahn, Markus
- Bioorganic & Medicinal Chemistry Letters, Vol. 20, Issue 18
Chelator-Free Synthesis of a Dual-Modality PET/MRI Agent
journal, October 2013
- Chen, Feng; Ellison, Paul A.; Lewis, Christina M.
- Angewandte Chemie International Edition, Vol. 52, Issue 50
Functionalized mesoporous silica materials for controlled drug delivery
journal, January 2012
- Yang, Piaoping; Gai, Shili; Lin, Jun
- Chemical Society Reviews, Vol. 41, Issue 9
In Vivo Tumor Targeting and Image-Guided Drug Delivery with Antibody-Conjugated, Radiolabeled Mesoporous Silica Nanoparticles
journal, September 2013
- Chen, Feng; Hong, Hao; Zhang, Yin
- ACS Nano, Vol. 7, Issue 10
In Vivo Integrity and Biological Fate of Chelator-Free Zirconium-89-Labeled Mesoporous Silica Nanoparticles
journal, July 2015
- Chen, Feng; Goel, Shreya; Valdovinos, Hector F.
- ACS Nano, Vol. 9, Issue 8
Production and chemical isolation procedure of positron-emitting isotopes of arsenic for environmental and medical applications
conference, January 2012
- Ellison, P. A.; Barnhart, T. E.; Engle, J. W.
- 14TH INTERNATIONAL WORKSHOP ON TARGETRY AND TARGET CHEMISTRY, AIP Conference Proceedings
Nuclear-Targeted Drug Delivery of TAT Peptide-Conjugated Monodisperse Mesoporous Silica Nanoparticles
journal, March 2012
- Pan, Limin; He, Qianjun; Liu, Jianan
- Journal of the American Chemical Society, Vol. 134, Issue 13
Impacts of Mesoporous Silica Nanoparticle Size, Pore Ordering, and Pore Integrity on Hemolytic Activity
journal, April 2010
- Lin, Yu-Shen; Haynes, Christy L.
- Journal of the American Chemical Society, Vol. 132, Issue 13
Works referencing / citing this record:
1,2-Benzenedithiol and Toluene-3,4-dithiol Arsenic(III) Complexes—Synthesis, Structure, Spectroscopic Characterization and Toxicological Studies
journal, October 2019
- Lyczko, Monika; Lyczko, Krzysztof; Majkowska-Pilip, Agnieszka
- Molecules, Vol. 24, Issue 21
Chemistry and radiochemistry of As, Re and Rh isotopes relevant to radiopharmaceutical applications: high specific activity radionuclides for imaging and treatment
journal, January 2017
- Feng, Yutian; Phelps, Tim E.; Carroll, Valerie
- Dalton Transactions, Vol. 46, Issue 42
Prevention of Deficit in Neuropsychiatric Disorders through Monitoring of Arsenic and Its Derivatives as Well as Through Bioinformatics and Cheminformatics
journal, April 2019
- Avram, Speranta; Udrea, Ana Maria; Negrea, Adina
- International Journal of Molecular Sciences, Vol. 20, Issue 8
PET radiometals for antibody labeling
journal, March 2018
- Aluicio-Sarduy, Eduardo; Ellison, Paul A.; Barnhart, Todd E.
- Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 61, Issue 9
Organic Arsenicals as Functional Motifs in Polymer and Biomaterials Science
journal, May 2018
- Tanaka, Joji; Davis, Thomas P.; Wilson, Paul
- Macromolecular Rapid Communications, Vol. 39, Issue 19
Targeted arsenite-loaded magnetic multifunctional nanoparticles for treatment of hepatocellular carcinoma
journal, February 2019
- Chi, Xiaoqin; Zhang, Renyuan; Zhao, Tian
- Nanotechnology, Vol. 30, Issue 17
Radioactive Nanomaterials for Multimodality Imaging
journal, March 2016
- Chen, Daiqin; Dougherty, Casey A.; Yang, Dongzhi
- Tomography, Vol. 2, Issue 1
Prevention of Deficit in Neuropsychiatric Disorders through Monitoring of Arsenic and Its Derivatives as Well as Through Bioinformatics and Cheminformatics
journal, April 2019
- Avram, Speranta; Udrea, Ana Maria; Negrea, Adina
- International Journal of Molecular Sciences, Vol. 20, Issue 8
1,2-Benzenedithiol and Toluene-3,4-dithiol Arsenic(III) Complexes—Synthesis, Structure, Spectroscopic Characterization and Toxicological Studies
journal, October 2019
- Lyczko, Monika; Lyczko, Krzysztof; Majkowska-Pilip, Agnieszka
- Molecules, Vol. 24, Issue 21