The development of a new production capability for 211At

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The development of a new production capability
for 211At 
Jerry Nolen, John Greene, Martin Alcorta, Bradley
Micklich, Shaofei Zhu, Chithra Nair, and Irshad
Ahmad, Physics Division Samuel Baker,
Environment, Safety, Quality Assurance
Division Argonne National Laboratory Chin-Tu
Chen, Sean S. H. Cheng, Leuwei Lo, and Patrick
Michael, Department of Radiology Anhui Wu, Muriel
Lainé, and Geoffrey Green, the Ben May Department
for Cancer Research University of Chicago Michael
Zalutsky, Duke University and University of
Chicago
Health physics support Fred Monette, Gordon
Johnson, and Angel Garcia
The 8th International Symposium on Targeted Alpha
Therapy

• This work was supported by the U.S. Department of
  Energy,
• Office of Nuclear Physics, under Contract No.
  DE-AC02-06CH11357.

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US Nuclear Science Advisory Committee Isotopes
Panel
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First recommendation of the NSAC-I panel
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Addressing the shortage identified by the NSAC-I
panel expanding accelerator-based production of
alpha-emitting isotopes

• Case 1 production of 225Ac/213Bi and 211Rn/211At
  generators by proton spallation of thorium
• Proposed by Argonne and ICGomes, Inc.
• Large yield predicted for protons above 100 MeV
• DOE funded for validation of 225Ac yields
• Collaboration of Argonne, FermiLab, ICGomes,
  Inc., and NorthStar Medical Isotopes
• Production test with FermiLab 8-GeV beam
  successfully completed in 2011
• Separation and purification chemistry was carried
  out at Argonne Chemistry Division
• Case 2 production of 211At at low energies with
  alpha or lithium beams
• Direct production of 211At (7-hour half-life) via
  the 209Bi(alpha,2n) reaction at alpha beam energy
  below 30 MeV to avoid 210At/210Po impurity
• Production of 211At via 211Rn generator (14-hour
  half-life) via the 209Bi(7Li,5n) reaction
• High power liquid-metal cooled target concept
  developed to enable extrapolation to high beam
  power
• Subject of proposed DOE/ONP RD at ANL/PHY/ATLAS

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The development of a new production capability
for 211At
Abstract Critically needed radionuclides for
cancer therapy include the alpha-emitter 211At
and potentially therapeutically useful
Auger-electron emitters. The ATLAS (Argonne
Tandem Linac Accelerator System) superconducting
linac at Argonne National Laboratory should be
suitable for the production of these
radionuclides. Our work is initially focusing on
demonstrating production capabilities for 211At
(7.2 h half-life) using the 209Bi(7Li,5n)211Rn or
the 209Bi(6Li,4n)211Rn reaction. Cross sections
for these reactions peak in the range of several
hundred mb 1 making production of 10s of mCi
per batch feasible using only a very small
percentage of the accelerator beam time.
Presently, RD with 211At is primarily at 3
facilities in the U.S. using the 209Bi(a,2n)211At
reaction at in-house cyclotrons. RD nation-wide
with 211At is limited due to its short half-life.
By using one of the lithium induced reactions,
the 211At daughter is extracted from the parent
211Rn, which has a half-life of 14 h,
significantly extending the time-frame for
effective distribution and use of this important
radionuclide. The impact of the half-life
difference is illustrated in the figure below.
ATLAS is an appropriate and flexible accelerator
for the production of medical isotopes because it
can provide beams of any ion including protons,
helium, lithium, and heavier ions with energies
adjustable over a wide range. An upgrade of the
accelerator and the shielding is in progress.
Following the completion of this work in the fall
of 2013, currents of ion beams up to 10 particle
microamps or more will be available. To fully
implement isotope production capability using
these more intense beams, a new irradiation cave
has been proposed. These combined upgrades will
enable yields of 100 mCi of 211Rn/211At using 10
hours of beam time per batch. 1. Meyer GJ,
Lambrecht RM, Excitation function for the
209Bi(7Li, 5n)211Rn nuclear reaction, Inter. J.
of App. Rad. and Isotopes, 31(1980)351-355.
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Excitation function for production of 211Rn
precursor of 211At
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The proposed development enables overnight
delivery of 211At to any facility in the U.S.
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Alpha vs. lithium advantages/disadvantages

• Alpha
• ? Cross section gives larger initial activity
• Target must be dissolved each run
• Dry distillation or wet extraction
• Lithium
• ? 14 hour half-life gt useful yield 1-3 days
  after production
• ? Continuous extraction of 211Rn from the target
• Simple physical extraction of 211At from the
  generator
• RD on lithium method in collaboration with
  Michael Zalutsky (Duke Chicago) with interested
  users at Univ. Chicago Comprehensive Cancer Center

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Location of proposed production cave in area 2
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Radiation handling at ATLAS
Glove box and hood at ATLAS
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Existing beam lines and apparatus at ATLAS
Scattering chamber at ATLAS
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Beamline and target assembly
Health physicist, Post-doc, Undergraduate Target/
helium plumbing/ heater assembly Havar
window 32 mg/cm2 Bi on Ni
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Carbon trap and corn-oil bubblers
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Activated carbon trap
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Counting 211Rn trapped in charcoal
(left)Counting 211At extracted from charcoal
(right)
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Target assembly, 211Rn trap, 211At elution
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X-ray Spectra of elution from charcoal
x-rays from 211At electron capture, no 207Po, no
211Rn
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Summary

• Clinically useful quantities of the alpha emitter
  211At can be produced with low energy light ions
  at the upgraded ANL/PHY ATLAS facility using
  small fraction of the annual beam time
• The production via the 211Rn/211At generator
  approach can greatly extend the national
  availability of this isotope by effectively
  doubling its life-time
• RD of this alternative method began recently
  with a test run at ATLAS
• Next step to use RGA to measure continuous
  release of Xe from hot, solid Bi