DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Proton induced production and radiochemical isolation of 44Ti from scandium metal targets for 44Ti/44Sc generator development

Abstract

Scandium-44 g (half-life 3.97 h) shows promise for application in positron emission tomography (PET), due to favorable decay parameters. One of the sources of 44gSc is the 44Ti/44gSc generator, which can conveniently provide this radioisotope on a daily basis at a diagnostic facility. Titanium-44 (half-life 60.0 a), in turn, can be obtained via proton irradiation of scandium metal targets. A substantial 44Ti product batch, however, requires high beam currents, long irradiation times and an elaborate chemical procedure for 44Ti isolation and purification. This study describes the production of a combined 175 MBq (4.7 mCi) batch yield of 44Ti in week long proton irradiations at the Los Alamos Isotope Production Facility (LANL-IPF) and the Brookhaven Linac Isotope Producer (BNL-BLIP). A two-step ion exchange chromatography based chemical separation method is introduced: first, a coarse separation of 44Ti via anion exchange sorption in concentrated HCl results in a 44Tc/Sc separation factor of 102–103. Here, a second, cation exchange based step in HCl media is then applied for 44Ti fine purification from residual Sc mass. In summary, this method yields a 90–97% 44Ti recovery with an overall Ti/Sc separation factor of ≥106.

Authors:
 [1];  [1];  [2];  [1];  [1];  [1];  [1]; ORCiD logo [1];  [1];  [2];  [2]; ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1]; ORCiD logo [1]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  2. Brookhaven National Lab. (BNL), Upton, NY (United States). Collider-Accelerator Dept.
Publication Date:
Research Org.:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States); Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC). Nuclear Physics (NP) (SC-26); USDOE Office of Science (SC), Nuclear Physics (NP)
OSTI Identifier:
1352426
Alternate Identifier(s):
OSTI ID: 1361398; OSTI ID: 1415250
Report Number(s):
LA-UR-16-29428; BNL-113861-2017-JA
Journal ID: ISSN 0969-8051; TRN: US1700548
Grant/Contract Number:  
AC52-06NA25396; SC00112704
Resource Type:
Accepted Manuscript
Journal Name:
Nuclear Medicine and Biology
Additional Journal Information:
Journal Volume: 50; Journal ID: ISSN 0969-8051
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Analytical Chemistry; Inorganic and Physical Chemistry; 43 PARTICLE ACCELERATORS; 44Ti; scandium target; ion exchange chromatography; proton irradiation; 44Ti/44gSc generator

Citation Formats

Radchenko, Valery, Engle, Jonathan Ward, Medvedev, Dmitri G., Maassen, Joel M., Naranjo, Cleo Micah, Unc, George A., Meyer, Catherine A.L., Mastren, Tara, Brugh, Mark, Mausner, Leonard, Cutler, Catherine S., Birnbaum, Eva R., John, Kevin Dale, Nortier, Francois Meiring, and Fassbender, Michael Ernst. Proton induced production and radiochemical isolation of 44Ti from scandium metal targets for 44Ti/44Sc generator development. United States: N. p., 2017. Web. doi:10.1016/j.nucmedbio.2017.03.006.
Radchenko, Valery, Engle, Jonathan Ward, Medvedev, Dmitri G., Maassen, Joel M., Naranjo, Cleo Micah, Unc, George A., Meyer, Catherine A.L., Mastren, Tara, Brugh, Mark, Mausner, Leonard, Cutler, Catherine S., Birnbaum, Eva R., John, Kevin Dale, Nortier, Francois Meiring, & Fassbender, Michael Ernst. Proton induced production and radiochemical isolation of 44Ti from scandium metal targets for 44Ti/44Sc generator development. United States. https://doi.org/10.1016/j.nucmedbio.2017.03.006
Radchenko, Valery, Engle, Jonathan Ward, Medvedev, Dmitri G., Maassen, Joel M., Naranjo, Cleo Micah, Unc, George A., Meyer, Catherine A.L., Mastren, Tara, Brugh, Mark, Mausner, Leonard, Cutler, Catherine S., Birnbaum, Eva R., John, Kevin Dale, Nortier, Francois Meiring, and Fassbender, Michael Ernst. Fri . "Proton induced production and radiochemical isolation of 44Ti from scandium metal targets for 44Ti/44Sc generator development". United States. https://doi.org/10.1016/j.nucmedbio.2017.03.006. https://www.osti.gov/servlets/purl/1352426.
@article{osti_1352426,
title = {Proton induced production and radiochemical isolation of 44Ti from scandium metal targets for 44Ti/44Sc generator development},
author = {Radchenko, Valery and Engle, Jonathan Ward and Medvedev, Dmitri G. and Maassen, Joel M. and Naranjo, Cleo Micah and Unc, George A. and Meyer, Catherine A.L. and Mastren, Tara and Brugh, Mark and Mausner, Leonard and Cutler, Catherine S. and Birnbaum, Eva R. and John, Kevin Dale and Nortier, Francois Meiring and Fassbender, Michael Ernst},
abstractNote = {Scandium-44 g (half-life 3.97 h) shows promise for application in positron emission tomography (PET), due to favorable decay parameters. One of the sources of 44gSc is the 44Ti/44gSc generator, which can conveniently provide this radioisotope on a daily basis at a diagnostic facility. Titanium-44 (half-life 60.0 a), in turn, can be obtained via proton irradiation of scandium metal targets. A substantial 44Ti product batch, however, requires high beam currents, long irradiation times and an elaborate chemical procedure for 44Ti isolation and purification. This study describes the production of a combined 175 MBq (4.7 mCi) batch yield of 44Ti in week long proton irradiations at the Los Alamos Isotope Production Facility (LANL-IPF) and the Brookhaven Linac Isotope Producer (BNL-BLIP). A two-step ion exchange chromatography based chemical separation method is introduced: first, a coarse separation of 44Ti via anion exchange sorption in concentrated HCl results in a 44Tc/Sc separation factor of 102–103. Here, a second, cation exchange based step in HCl media is then applied for 44Ti fine purification from residual Sc mass. In summary, this method yields a 90–97% 44Ti recovery with an overall Ti/Sc separation factor of ≥106.},
doi = {10.1016/j.nucmedbio.2017.03.006},
journal = {Nuclear Medicine and Biology},
number = ,
volume = 50,
place = {United States},
year = {Fri Apr 07 00:00:00 EDT 2017},
month = {Fri Apr 07 00:00:00 EDT 2017}
}

Journal Article:

Citation Metrics:
Cited by: 24 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Evaluation of the first 44Sc-labeled Affibody molecule for imaging of HER2-expressing tumors
journal, February 2017


44 Sc: An Attractive Isotope for Peptide-Based PET Imaging
journal, July 2014

  • Hernandez, Reinier; Valdovinos, Hector F.; Yang, Yunan
  • Molecular Pharmaceutics, Vol. 11, Issue 8
  • DOI: 10.1021/mp500343j

Imaging of Protein Synthesis: In Vitro and In Vivo Evaluation of 44Sc-DOTA-Puromycin
journal, May 2012

  • Eigner, Sebastian; Vera, Denis R. Beckford; Fellner, Marco
  • Molecular Imaging and Biology, Vol. 15, Issue 1
  • DOI: 10.1007/s11307-012-0561-3

Promising prospects of 44mSc/44Sc as an in vivo generator: Biological evaluation and PET images
journal, August 2014


Radiochemical purification of no-carrier-added scandium-47 for radioimmunotherapy
journal, December 1998


Production and purification of Scandium-47: A potential radioisotope for cancer theranostics
journal, December 2016


Generator-based PET radiopharmaceuticals for molecular imaging of tumours: on the way to THERANOSTICS
journal, January 2011

  • Rösch, Frank; Baum, Richard P.
  • Dalton Transactions, Vol. 40, Issue 23
  • DOI: 10.1039/c0dt01504k

Promising Prospects for 44Sc-/47Sc-Based Theragnostics: Application of 47Sc for Radionuclide Tumor Therapy in Mice
journal, July 2014


44Sc-DOTA-BN[2-14]NH2 in comparison to 68Ga-DOTA-BN[2-14]NH2 in pre-clinical investigation. Is 44Sc a potential radionuclide for PET?
journal, December 2012


44Sc for labeling of DOTA- and NODAGA-functionalized peptides: preclinical in vitro and in vivo investigations
journal, May 2016

  • Domnanich, Katharina A.; Müller, Cristina; Farkas, Renata
  • EJNMMI Radiopharmacy and Chemistry, Vol. 1, Issue 1
  • DOI: 10.1186/s41181-016-0013-5

Macrocyclic complexes of scandium radionuclides as precursors for diagnostic and therapeutic radiopharmaceuticals
journal, February 2011


Radiolabeling of DOTATOC with the long-lived positron emitter 44Sc
journal, June 2012

  • Pruszyński, Marek; Majkowska-Pilip, Agnieszka; Loktionova, Natalia S.
  • Applied Radiation and Isotopes, Vol. 70, Issue 6
  • DOI: 10.1016/j.apradiso.2012.03.005

Current advances in ligand design for inorganic positron emission tomography tracers 68 Ga, 64 Cu, 89 Zr and 44 Sc
journal, January 2016

  • Price, Thomas W.; Greenman, John; Stasiuk, Graeme J.
  • Dalton Transactions, Vol. 45, Issue 40
  • DOI: 10.1039/C5DT04706D

Study of the excitation functions for 43K, 43,44,44mSc and 44Ti by proton irradiation on 45Sc up to 37MeV
journal, March 2009

  • Daraban, L.; Adam Rebeles, R.; Hermanne, A.
  • Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, Vol. 267, Issue 5
  • DOI: 10.1016/j.nimb.2009.01.010

Nuclear interactions of 45Sc and 68Zn with protons of medium energy
journal, July 1970


Cross sections for Sc 45 ( p ,2 n ) 44 Ti and related reactions
journal, October 1996


Production of scandium-44m and scandium-44g with deuterons on calcium-44: cross section measurements and production yield calculations
journal, August 2015


Cyclotron production of high purity 44m,44 Sc with deuterons from 44 CaCO 3 targets
journal, June 2015


Cyclotron production of 44Sc: From bench to bedside
journal, September 2015


Cyclotron produced 44gSc from natural calcium
journal, August 2012


44gSc production using a water target on a 13MeV cyclotron
journal, May 2014


Cyclotron production of 44 Sc for clinical application
journal, May 2013

  • Krajewski, Seweryn; Cydzik, Izabela; Abbas, Kamel
  • Radiochimica Acta, Vol. 101, Issue 5
  • DOI: 10.1524/ract.2013.2032

Scandium-44: Benefits of a Long-Lived PET Radionuclide Available from the 44Ti/44Sc Generator System
journal, June 2012


A 44Ti/44Sc radionuclide generator for potential application of 44Sc-based PET-radiopharmaceuticals
journal, January 2010

  • Filosofov, D. V.; Loktionova, N. S.; Rösch, Frank
  • Radiochimica Acta, Vol. 98, Issue 3
  • DOI: 10.1524/ract.2010.1701

Preparation of a radioactive target
journal, March 1999

  • Lange, R.; D'Auria, J.; Giesen, U.
  • Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, Vol. 423, Issue 2-3
  • DOI: 10.1016/S0168-9002(98)01289-3

[sup 45]Ti extraction using hydroxamate resin
conference, January 2012

  • Gagnon, K.; Severin, G. W.; Barnhart, T. E.
  • 14TH INTERNATIONAL WORKSHOP ON TARGETRY AND TARGET CHEMISTRY, AIP Conference Proceedings
  • DOI: 10.1063/1.4773970

Separation of 44Ti from proton irradiated scandium by using solid-phase extraction chromatography and design of 44Ti/44Sc generator system
journal, December 2016


Selenium-72 formation via natBr(p,x) induced by 100MeV Protons: Steps towards a novel 72Se/72As generator system
journal, April 2012


Proton beam simulation with MCNPX: Gallium metal activation estimates below 30MeV relevant to the bulk production of 68Ge and 65Zn
journal, August 2007

  • Fassbender, M.; Arzumanov, A.; Jamriska, D. J.
  • Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, Vol. 261, Issue 1-2
  • DOI: 10.1016/j.nimb.2007.03.099

Proton irradiation parameters and chemical separation procedure for the bulk production of high-specific-activity 186g Re using WO 3 targets
journal, May 2013

  • Fassbender, M. E.; Ballard, B.; Birnbaum, E. R.
  • Radiochimica Acta, Vol. 101, Issue 5
  • DOI: 10.1524/ract.2013.2031

Works referencing / citing this record:

New developments in the production of theranostic pairs of radionuclides
journal, October 2018

  • Qaim, Syed M.; Scholten, Bernhard; Neumaier, Bernd
  • Journal of Radioanalytical and Nuclear Chemistry, Vol. 318, Issue 3
  • DOI: 10.1007/s10967-018-6238-x

Comparison of scandium-44 g with other PET radionuclides in pre-clinical PET phantom imaging
journal, December 2019


Comparison of scandium-44 g with other PET radionuclides in pre-clinical PET phantom imaging
journal, December 2019