Photonuclear production, chemistry, and in vitro evaluation of the theranostic radionuclide ⁴⁷Sc

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 (⁴⁷Sc, T_1/2 = 3.35 days), which can be used for targeted radiotherapy and may be paired with the positron emitting radionuclides, ⁴³Sc (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 ⁴⁷Sc via the ⁴⁸Ti(γ,p)⁴⁷Sc reaction using an electron linear accelerator (eLINAC), separation and purification of ⁴⁷Sc, the radiolabeling of somatostatin receptor-targeting peptide DOTATOC with ⁴⁷Sc, and in vitro receptor-mediated binding of [⁴⁷Sc]Sc-DOTATOC in AR42J somatostatin receptor subtype two (SSTR2) expressing rat pancreatic tumor cells. Results: The rate of ⁴⁷Sc production in a stack of natural titanium foils (n = 39) was 8 × 10⁷ Bq/mA·h (n = 3). Irradiated target foils were dissolved in 2.0 M H₂SO₄ under reflux. After dissolution, trivalent ⁴⁷Sc 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 ⁴⁷Sc recovery (n = 9) was (77 ± 7)%. A radiolabeling yield of > 99.9% of [⁴⁷Sc]Sc-DOTATOC (0.384 mg in 0.3 mL) was achieved using 1.7 MBq of ⁴⁷Sc. Blocking studies using Octreotide illustrated receptor-mediated uptake of [⁴⁷Sc]Sc-DOTATOC in AR42J cells. Conclusions: ⁴⁷Sc can be produced via the ⁴⁸Ti(γ,p)⁴⁷Sc 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.