Photonuclear production, chemistry, and in vitro evaluation of the theranostic radionuclide $^{47}$Sc

Abstract

Background: In molecular imaging and nuclear medicine, theranostic agents that integrate radionuclide pairs are successfully being used for individualized care, which has led to rapidly growing interest in their continued development. These compounds, which are radiolabeled with one radionuclide for imaging and a chemically identical or similar radionuclide for therapy, may improve patient-specific treatment and outcomes by matching the properties of different radionuclides with a targeting vector for a particular tumor type. One proposed theranostic radionuclide is scandium-47 ($^{47}$Sc, T$_{1/2}$ = 3.35 days), which can be used for targeted radiotherapy and may be paired with the positron emitting radionuclides, $^{43}$Sc (T$_{1/2}$ = 3.89 h) and 44Sc (T$_{1/2}$ = 3.97 h) for imaging. The aim of this study was to investigate the photonuclear production of $^{47}$Sc via the $^{48}$Ti(γ,p)$^{47}$Sc reaction using an electron linear accelerator (eLINAC), separation and purification of $^{47}$Sc, the radiolabeling of somatostatin receptor-targeting peptide DOTATOC with $^{47}$Sc, and in vitro receptor-mediated binding of [$^{47}$Sc]Sc-DOTATOC in AR42J somatostatin receptor subtype two (SSTR2) expressing rat pancreatic tumor cells. Results: The rate of $^{47}$Sc production in a stack of natural titanium foils (n = 39) was 8 × 10$^7$ Bq/mA·h (n = 3). Irradiated target foils were dissolved in 2.0 M H$_2$SO$_4$ under reflux. After dissolution, trivalent $^{47}$Sc ions were separated from natural Ti using AG MP-50 cation exchange resin. The recovered 47Sc was then purified using CHELEX 100 ion exchange resin. The average decay-corrected two-step $^{47}$Sc recovery (n = 9) was (77 ± 7)%. A radiolabeling yield of > 99.9% of [$^{47}$Sc]Sc-DOTATOC (0.384 mg in 0.3 mL) was achieved using 1.7 MBq of $^{47}$Sc. Blocking studies using Octreotide illustrated receptor-mediated uptake of [$^{47}$Sc]Sc-DOTATOC in AR42J cells. Conclusions: $^{47}$Sc can be produced via the $^{48}$Ti(γ,p)$^{47}$Sc reaction and separated from natural Ti targets with a yield and radiochemical purity suitable for radiolabeling of peptides for in vitro studies. The data in this work supports the potential use of eLINACs for studies of photonuclear production of medical radionuclides and the future development of high-intensity eLINAC facilities capable of producing relevant quantities of carrier-free radionuclides currently inaccessible via routine production pathways or limited due to costly enriched targets.