Cyclotron production and imaging properties of scandium-44

  • Author / Creator
    Ferguson, Denis Simon
  • Radioisotopes of scandium have been proposed as potential candidates for radiotheranostics, the combination of targeted imaging and therapy of cancer. Radiolabelling specific targeting vectors with positron emitting radioisotopes (43Sc, 44Sc) provides a quantitative measure of the disease through molecular imaging; the information gained from the diagnostic study can be leveraged to improve treatment with an analogue of the same targeting vector with a therapeutic radionuclide (47Sc) to deliver dose to the disease. The development of a reliable supply of 44Sc was achieved for this thesis, and this has enabled preclinical research studies on its production and imaging.
    Experimental surveys are often conducted to determine the viability of production routes for emerging radionuclides. Predictive tools for calculating radionuclidic yield can help curtail the cost of target materials and focus irradiations during experimental surveys. Improvements in Geant4 modelling of low energy proton-induced reactions has sparked interest in using simulations for radionuclide yield calculations. Simulations of thick target yields from the proton irradiation of natural calcium have been compared with calculations based on experimental cross-section data. Measurements of thick target yield were made at energies between 12 and 18 MeV, revealing that Geant4 could accurately predict the yield of several contaminants produced during irradiation within 10 %, including 46Sc, 47Sc and 48Sc. With further validation, Geant4 could serve as a useful tool in target development.
    The decay characteristics of radionuclides in PET studies can impact image reconstruction. The first measurements of standard performance metrics for 44Sc were made using the NEMA image quality phantom in the Siemens Inveon small-animal PET scanner. These measurements were compared with 18F, 64Cu and 68Ga; the recovery coefficients and the spill-over ratio in water were related to the mean positron emission energy, with the long-range positron emitter 68Ga having lower recovery coefficients and greater spill-over ratio than the short-range positron emitters 64Cu and 18F. 44Sc demonstrated intermediate behaviour between 18F and 68Ga, with greater recovery coefficients than 68Ga. Derenzo and NEC phantoms were also used for comparisons, which revealed that the NEC rate for 44Sc increases at a lower rate than 18F and 68Ga as a function of activity in the field-of-view.
    Radiolabeled peptides play a central role in nuclear medicine as radiotheranostics for targeted imaging and therapy of cancer; the gastrin-releasing peptide receptor has been demonstrated to be overexpressed in several cancers and a metabolically stabilized antagonist BBN2 has demonstrated potential for specific targeting. 44Sc and 68Ga were used to radiolabel DOTA complexes of BBN2 and the radiopeptides were prepared in high radiochemical yields. High GRPR binding affinity in vitro was found for both peptides, motivating in vivo biodistribution studies in MCF7 breast and PC3 prostate cancer models. PET imaging revealed low tumor uptake of both radiotracers in MCF7 xenografts, whereas high tumor uptake and retention was found for both radiopeptides in PC3 tumors. 68Ga- and 44Sc- radiolabelled peptides displayed comparable tumor uptake and retention, demonstrating the potential use of 44Sc as a diagnostic surrogate.

  • Subjects / Keywords
  • Graduation date
    Spring 2022
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.