Nuclide production and imaging applications of ²²⁵Ac for targeted alpha therapy
department or school: Science, Faculty of
department or school: Physics and Astronomy, Department of
data provider: DSpace
degree campus: UBCV
creator: Robertson, Andrew Kyle Henderson
issued: 2020-12-24T19:33:52Z
issued: 2020
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Targeted alpha therapies using actinium-225 (²²⁵Ac, t₁/₂ = 9.9 d) can treat advanced metastatic disease, yet insufficient ²²⁵Ac availability limits their development (63 GBq/year is produced globally via ²²⁹Th generators). This thesis describes efforts to produce ²²⁵Ac and apply multi-nuclide SPECT imaging in preclinical evaluation of ²²⁵Ac-radiopharmaceuticals. Initial ²²⁵Ac production used ᴺᵃᵗU-spallation-produced and mass-separated ion beams, producing up to 8.6 MBq of ²²⁵Ra (an ²²⁵Ac parent) and 18 MBq of ²²⁵Ac. This material helped characterize the performance of ²²⁵Ac decay chain imaging on a microSPECT/PET/CT scanner in terms of contrast recovery, spatial resolution, and noise. Larger ²²⁵Ac quantities were produced via thorium target irradiation with a 438 MeV, 72 μA proton beam for 36 hours, producing (521 ± 18) MBq of ²²⁵Ac and (91 ± 14) MBq of ²²⁵Ra. These irradiations enabled ²³²Th(p,x) cross sections measurements for ²²⁵Ac, ²²⁵Ra, and ²²⁷Ac: (13.3 ± 1.2) mb, (4.2 ± 0.4) mb, and (17.7 ± 1.7) mb, respectively. Thirty-five other cross sections were measured and compared to FLUKA simulations; measured and calculated values generally agree within a factor of two. Ac separation from irradiated thorium and co-produced radioactive by-products used a thorium peroxide precipitation followed by cation exchange and extraction chromatography. Studies showed this method separates Ac from most elements, providing a directly-produced Ac product (²²⁷˒²²⁵Ac†) with measured ²²⁷Ac content of (0.15 ± 0.04)%, a hazardous long-lived (t₁/₂ = 21.8 y) impurity with prohibitively low waste disposal limits. A second, indirectly-produced ²²⁵Ra/²²⁵Ac-generator-derived Ac product (²²⁵Ac*) with ²²⁷Ac content of <7.5x10⁻⁵% was also obtained. The thorium target design, the simulations benchmarked against newly measured cross sections, and the precipitation-based thorium target processing method are separate novel contributions that together form the first demonstration of ²²⁵Ac* producti…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/76900
note: Nuclide Production and ImagingApplications of 225Ac for TargetedAlpha TherapybyAndrew Kyle Henderson RobertsonBSc (Hons.), The University of Victoria, 2013A THESIS SUBMITTED IN PARTIAL FULFILLMENT OFTHE REQUIREMENTS FOR THE DEGREE OFDOCTOR OF PHILOSOPHYinThe Faculty of Graduate and Postdoctoral Studies(Physics)THE UNIVERSITY OF BRITISH COLUMBIA(Vancouver)December 2020c© Andrew Kyle Henderson Robertson 2020The following individuals certify that they have read, and recommend tothe Faculty of Graduate and Postdoctoral Studies for acceptance, the thesisentitled:Nuclide Production and Imaging Applications of 225Ac forTargeted Alpha Therapysubmitted by Andrew Kyle Henderson Robertson in partial fulfillmentof the requirements forthe degree of Doctor of Philosophyin PhysicsExamining Committee:Paul Schaffer, RadiologyCo-supervisorVesna Sossi, Physics and AstronomyCo-supervisorStefan Reinsberg, Physics and AstronomySupervisory Committee MemberRob Kiefl, Physics and AstronomySupervisory Committee MemberDouglas Bryman, Physics and AstronomyUniversity ExaminerLaurel Schafer, ChemistryUniversity ExaminerKen Czerwinksi, University of WashingtonExternal ExaminerHarry Brumer, ChemistryChairiiAbstractTargeted alpha therapies using actinium-225 (225Ac, t1/2 = 9.9 d) cantreat advanced metastatic disease, yet insufficient 225Ac availability lim-its their development (63 GBq/year is produced globally via 229Th genera-tors). This thesis describes efforts to produce 225Ac and apply multi-nuclideSPECT imaging in preclinical evaluation of 225Ac-radiopharmaceuticals.Initial 225Ac production used NatU-spallation-produced and mass-separatedion beams, producing up to 8.6 MBq of 225Ra (an 225Ac parent) and 18MBq of 225Ac. This material helped characterize the performance of 225Acdecay chain imaging on a microSPECT/PET/CT scanner in terms of con-trast recovery, spatial resolution, and noise. Larger 225Ac quantities wereproduced via thorium target irradiation with a 438 MeV, 72 µA protonbeam for 36…
has type: Thesis/Dissertation
date issued: 2021-05
is shown at: 10.14288/1.0395400
language: eng
degree discipline: Physics
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/76900