title: Bulk production and evaluation of high specific activity186gRe for cancer therapy using enriched186WO3targets in a proton beam.
abstract: BACKGROUND
  Rhenium-186g (t1/2= 3.72 d) is a β-emitting isotope suitable for theranostic applications. Current production methods rely on reactor production by way of the reaction185Re(n,γ)186gRe, which results in low specific activities limiting its use for cancer therapy. Production via charged particle activation of enriched186W results in a186gRe product with a higher specific activity, allowing it to be used more broadly for targeted radiotherapy applications. This targets the unmet clinical need for more efficient radiotherapeutics.
  
  
  METHODS
  A target consisting of highly enriched, pressed186WO3was irradiated with protons at the Los Alamos National Laboratory Isotope Production Facility (LANL-IPF) to evaluate186gRe product yield and quality. LANL-IPF was operated in a dedicated nominal 40 MeV mode. Alkaline dissolution followed by anion exchange chromatography was used to isolate186gRe from the target material. Phantom and radiolabeling studies were conducted with the produced186gRe activity.
  
  
  RESULTS
  A186gRe batch yield of 1.38 ± 0.09 MBq/μAh or 384.9 ± 27.3 MBq/C was obtained after 16.5 h in a 205 μA average/230μA maximum current proton beam. The chemical recovery yield was 93% and radiolabeling was achieved with efficiencies ranging from 60-80%. True specific activity of186gRe at EOB was determined via ICP-AES and amounted to 0.788 ± 0.089 GBq/μg (0.146 ± 0.017 GBq/nmol), which is approximately seven times higher than the product obtained from neutron capture in a reactor. Phantom studies show similar imaging quality to the gold standard99mTc.
  
  
  CONCLUSIONS
  We report a preliminary study of the large-scale production and novel anion exchange based chemical recovery of high specific activity186gRe from enriched186WO3targets in a high-intensity proton beam with exceptional chemical recovery and radiochemical purity.
authors.affiliation: Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, 87545.
authors.forename: Tara
authors.initials: T
authors.lastname: Mastren
authors.affiliation: Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, 87545.
authors.forename: Valery
authors.initials: V
authors.lastname: Radchenko
authors.affiliation: Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, 87545.
authors.forename: Hong T
authors.initials: HT
authors.lastname: Bach
authors.affiliation: Department of Radiation Oncology, University of Washington, Seattle, WA, 98105.
authors.forename: Ethan R
authors.initials: ER
authors.lastname: Balkin
authors.affiliation: Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, 87545.
authors.forename: Eva R
authors.initials: ER
authors.lastname: Birnbaum
authors.affiliation: Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, 87545.
authors.forename: Mark
authors.initials: M
authors.lastname: Brugh
authors.affiliation: Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, 87545.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Engle
authors.affiliation: Department of Chemistry, University of Missouri-Columbia, Columbia, MO, 65211.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Gott
authors.affiliation: Research Reactor Center, University of Missouri-Columbia, Columbia, MO, 65211.
authors.forename: James
authors.initials: J
authors.lastname: Guthrie
authors.affiliation: Research Reactor Center, University of Missouri-Columbia, Columbia, MO, 65211.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Hennkens
authors.affiliation: Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, 87545.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: John
authors.affiliation: Research Reactor Center, University of Missouri-Columbia, Columbia, MO, 65211.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Ketring
authors.affiliation: Research Reactor Center, University of Missouri-Columbia, Columbia, MO, 65211.
authors.forename: Marina
authors.initials: M
authors.lastname: Kuchuk
authors.affiliation: Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, 87545.
authors.forename: Joel R
authors.initials: JR
authors.lastname: Maassen
authors.affiliation: Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, 87545.
authors.forename: Cleo M
authors.initials: CM
authors.lastname: Naranjo
authors.affiliation: Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, 87545.
authors.forename: F Meiring
authors.initials: FM
authors.lastname: Nortier
authors.affiliation: Department of Chemistry, University of Missouri-Columbia, Columbia, MO, 65211.
authors.forename: Tim E
authors.initials: TE
authors.lastname: Phelps
authors.affiliation: Department of Chemistry, University of Missouri-Columbia, Columbia, MO, 65211.
authors.forename: Silvia S
authors.initials: SS
authors.lastname: Jurisson
authors.affiliation: Department of Radiation Oncology, University of Washington, Seattle, WA, 98105.
authors.forename: D Scott
authors.initials: DS
authors.lastname: Wilbur
authors.affiliation: Chemistry Division, Los Alamos National Laboratory, Los Alamos, NM, 87545. Electronic address: mifa@lanl.gov.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Fassbender
mesh_terms: D007553:Isotope Labeling; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D010087:Oxides / Q000737:chemistry*; D019047:Phantoms, Imaging; D061766:Proton Therapy / Q000379:methods*; D011854:Radiochemistry / Q000379:methods*; D012211:Rhenium / Q000737:chemistry* / Q000627:therapeutic use*; D015899:Tomography, Emission-Computed, Single-Photon; D014414:Tungsten / Q000737:chemistry*
chemical_list: D010087:Oxides; D012211:Rhenium; C511604:tungsten oxide; D014414:Tungsten
keywords: (186)WO(3) target; (186g)Re; High specific activity; Radiolabeling; SPECT phantom images; Theranostic