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, T1/2 = 3.35 days), which can be used for targeted radiotherapy and may be paired with the positron emitting radionuclides, 43Sc (T1/2 = 3.89 h) and 44Sc (T1/2 = 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.

Production of 15O for Medical Applications via the 16O(γ,n)15O Reaction.

15O (half-life, 122 s) is a useful radionuclide for PET applications. Current production of 15O typically makes use of the 14N(d,n)15O, 15N(p,n)15O, or 16O(p,pn)15O reactions using an accelerator. A novel approach for the production of 15O is via the 16O(γ,n)15O reaction using an electron linear accelerator. Photonuclear reactions using an electron linear accelerator may allow for feasible and economical production of 15O compared with the current methods. Methods: In this work, experiments using a repurposed Clinac were conducted using oxygen-containing alumina as a target material to study the production rate of 15O. Additional studies were conducted using a water target cell. Simulations using Geant4 were conducted to predict the activity and power dissipation in the target. Results: Bremsstrahlung radiation from the electron beam, and consequently 15O production via photonuclear reactions, is enhanced when a high-Z material, tungsten, is placed in front of the target. The alumina irradiations provided preliminary data to optimize the beam parameters and target configuration. The optimal thickness of tungsten was 1.4 mm for both the simulated and the measured studies of alumina. Simulations of irradiated water targets showed that tungsten thicker than 1.4 mm resulted in fewer photons available to activate the water; thus, a higher current was required to achieve a fixed dose. Alternatively, for a constant tungsten thickness, more power was deposited in the target with increasing beam energy, requiring a lower current to achieve a fixed dose. Actual irradiations of a water target yielded a quantity of 15O in the water that was consistent with expectations based on irradiations of alumina. Conclusion: Several parameters should be considered regarding the photonuclear production of 15O for an average patient dose of 1,850 MBq (50 mCi) in 10 mL. This work illustrates a variety of machine parameters capable of achieving a reasonable patient dose. Our simulations show that the power deposited in the target for these parameters is less than that in commercially operated cyclotron targets for the production of 18F. Thus, this work demonstrates that the photonuclear production of 15O may be a new production path for this useful radionuclide.

Searching for the rules that govern hadron construction.

Just as quantum electrodynamics describes how electrons are bound in atoms by the electromagnetic force, mediated by the exchange of photons, quantum chromodynamics (QCD) describes how quarks are bound inside hadrons by the strong force, mediated by the exchange of gluons. QCD seems to allow hadrons constructed from increasingly many quarks to exist, just as atoms with increasing numbers of electrons exist, yet such complex constructions seemed, until recently, not to be present in nature. Here we describe advances in the spectroscopy of mesons that are refining our understanding of the rules for predicting hadron structure from QCD.