Advisor(s)
Suzanne Lapi
Committee Member(s)
Aaron Lucius
Benjamin Larimer
Jonathan Burns
Jonathan McConathy
Richard Dluhy
School
College of Arts and Sciences
Document Type
Dissertation
Department (new version)
Chemistry
Date of Award
1-6-2025
Abstract
In nuclear medicine, theranostics utilizes radionuclide pairs for diagnosis and therapy. Radioscandium isotopes (43Sc, 44Sc, and 47Sc) offer a promising alternative to the 68Ga/177Lu theranostic pair due to their identical radiolabeling conditions, complexes and in vivo pharmacokinetics. 43Sc (t1/2=3.89h, β+=88%) and 44Sc (t1/2 =3.97h. β+=94.3%) are suitable for Positron Emission Tomography (PET) imaging whereas 47Sc (t1/2=3.3d. Eβ-ave=162keV) is suitable for targeted radiotherapy and Single Photon Emission Computed Tomography (SPECT). These isotopes require production routes that lead to high radionuclidic purity and radiochemistry development for incorporation into radiopharmaceuticals. This study explores the production, purification, and application of these isotopes. The proton irradiation of enriched [46Ti]TiO2 and enriched [50Ti]TiO2 was used to investigate the production yields and purity of the produced radioscandium nuclides, as well as optimization of the purification method to high chemically pure radioscandium. Enriched [46Ti]TiO2 and [50Ti]TiO2 led to high purity 43Sc(98.8±0.3% radionuclidic purity) and 47Sc(91.5±0.6% radionuclidic purity). Nuclear cross sections of proton-induced reactions at 24 MeV on vanadium targets were characterized and used to optimize 47Sc production. Novel vanadium cyclotron targets and purification methods were developed for high purity 47Sc production (99.5±0.2% radionuclidic purity). The produced 43Sc and 47Sc were used for downstream chemical applications by complexation with PSMA-617 for a proof-of-concept theranostic study. Stability and binding were characterized in vitro. In vivo studies included PET imaging of [43Sc]Sc-PSMA-617 in PSMA+ and PSMA- tumor models, SPECT imaging of [47Sc]Sc-PSMA-617 in PSMA+ models, and a therapy study involving PET imaging of [43Sc]Sc-PSMA-617 before the single-dose administration of [47Sc]Sc-PSMA-617. The results show two promising routes for radioscandium production: enriched titanium dioxide targets and natural vanadium targets. All targets yield high radionuclidically pure 43Sc or 47Sc, at >90%. Two purification methods resulted in high recovery of radioscandium using BDGA or MP-50 resin. The produced radioscandium was used to radiolabel PSMA-617 and to investigate the theranostic potential of 43Sc and 47Sc. [43Sc]Sc-PSMA-617 and [47Sc]Sc-PSMA-617 showed specificity to PSMA receptors both in vitro and in vivo. The methods developed here can be used for future work in continued scaled-up production of either target and validated 43Sc and 47Sc as a theranostic pair for preclinical and potentially clinical applications.
ProQuest ID
Recommended Citation
Cingoranelli, Shelbie Jaylene, "Production And Radiochemistry Of Theranostic Radioscandium Nuclides" (2025). All ETDs from UAB. 7242.
https://digitalcommons.library.uab.edu/etd-collection/7242
