title: Radioisotopic Purity of Sodium Pertechnetate 99mTc Produced with a Medium-Energy Cyclotron: Implications for Internal Radiation Dose, Image Quality, and Release Specifications.
abstract: Cyclotron production of 99mTc is a promising route to supply 99mTc radiopharmaceuticals. Higher 99mTc yields can be obtained with medium-energy cyclotrons in comparison to those dedicated to PET isotope production. To take advantage of this capability, evaluation of the radioisotopic purity of 99mTc produced at medium energy (20-24 MeV) and its impact on image quality and dosimetry was required.
  
  
  METHODS
  Thick 100Mo (99.03% and 99.815%) targets were irradiated with incident energies of 20, 22, and 24 MeV for 2 or 6 h. The targets were processed to recover an effective thickness corresponding to approximately 5-MeV energy loss, and the resulting sodium pertechnetate 99mTc was assayed for chemical, radiochemical, and radionuclidic purity. Radioisotopic content in final formulation was quantified using γ-ray spectrometry. The internal radiation dose for 99mTc-pertechnetate was calculated on the basis of experimentally measured values and biokinetic data in humans. Planar and SPECT imaging were performed using thin capillary and water-filled Jaszczak phantoms.
  
  
  RESULTS
  Extracted sodium pertechnetate 99mTc met all provisional quality standards. The formulated solution for injection had a pH of 5.0-5.5, contained greater than 98% of radioactivity in the form of pertechnetate ion, and was stable for at least 24 h after formulation. Radioisotopic purity of 99mTc produced with 99.03% enriched 100Mo was greater than 99.0% decay corrected to the end of bombardment (EOB). The radioisotopic purity of 99mTc produced with 99.815% enriched 100Mo was 99.98% or greater (decay corrected to the EOB). The estimated dose increase relative to 99mTc without any radionuclidic impurities was below 10% for sodium pertechnetate 99mTc produced from 99.03% 100Mo if injected up to 6 h after the EOB. For 99.815% 100Mo, the increase in effective dose was less than 2% at 6 h after the EOB and less than 4% at 15 h after the EOB when the target was irradiated at an incident energy of 24 MeV. Image spatial resolution and contrast with cyclotron-produced 99mTc were equivalent to those obtained with 99mTc eluted from a conventional generator.
  
  
  CONCLUSIONS
  Clinical-grade sodium pertechnetate 99mTc was produced with a cyclotron at medium energies. Quality control procedures and release specifications were drafted as part of a clinical trial application that received approval from Health Canada. The results of this work are intended to contribute to establishing a regulatory framework for using cyclotron-produced 99mTc in routine clinical practice.
authors.affiliation: Sherbrooke Molecular Imaging Center, CRCHUS, Sherbrooke, Quebec, Canada Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada; and svetlana.v.selivanova@usherbrooke.ca.
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Selivanova
authors.affiliation: Sherbrooke Molecular Imaging Center, CRCHUS, Sherbrooke, Quebec, Canada.
authors.forename: Éric
authors.initials: É
authors.lastname: Lavallée
authors.affiliation: Sherbrooke Molecular Imaging Center, CRCHUS, Sherbrooke, Quebec, Canada.
authors.forename: Helena
authors.initials: H
authors.lastname: Senta
authors.affiliation: Sherbrooke Molecular Imaging Center, CRCHUS, Sherbrooke, Quebec, Canada.
authors.forename: Lyne
authors.initials: L
authors.lastname: Caouette
authors.affiliation: Advanced Cyclotron Systems Inc., Richmond, British Columbia, Canada.
authors.forename: Jayden A
authors.initials: JA
authors.lastname: Sader
authors.affiliation: Advanced Cyclotron Systems Inc., Richmond, British Columbia, Canada.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: van Lier
authors.affiliation: Advanced Cyclotron Systems Inc., Richmond, British Columbia, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zyuzin
authors.affiliation: Sherbrooke Molecular Imaging Center, CRCHUS, Sherbrooke, Quebec, Canada Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada; and.
authors.forename: Johan E
authors.initials: JE
authors.lastname: van Lier
authors.affiliation: Sherbrooke Molecular Imaging Center, CRCHUS, Sherbrooke, Quebec, Canada Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada; and.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Guérin
authors.affiliation: Sherbrooke Molecular Imaging Center, CRCHUS, Sherbrooke, Quebec, Canada Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada; and.
authors.forename: Éric
authors.initials: É
authors.lastname: Turcotte
authors.affiliation: Sherbrooke Molecular Imaging Center, CRCHUS, Sherbrooke, Quebec, Canada Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada; and.
authors.forename: Roger
authors.initials: R
authors.lastname: Lecomte
mesh_terms: D017357:Cyclotrons; D004340:Drug Contamination; D007554:Isotopes; D008982:Molybdenum; D019047:Phantoms, Imaging; D049268:Positron-Emission Tomography; D011786:Quality Control; D011829:Radiation Dosage; D011854:Radiochemistry / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000493:pharmacokinetics; D013670:Sodium Pertechnetate Tc 99m / Q000737:chemistry / Q000302:isolation & purification* / Q000493:pharmacokinetics
chemical_list: D007554:Isotopes; D019275:Radiopharmaceuticals; D008982:Molybdenum; D013670:Sodium Pertechnetate Tc 99m
keywords: 99mTc-pertechnetate; cyclotron; dosimetry; imaging; radionuclidic and radioisotopic purity