Cyclotron production of (44)Sc: From bench to bedside

(44)Sc, a PET radionuclide, has promising decay characteristics (T1/2 = 3.97 h, Eβ(+)av = 632 keV) for nuclear imaging and is an attractive alternative to the short-lived (68)Ga (T1/2 = 68 min, Eβ(+)av = 830 keV). The aim of this study was the optimization of the (44)Sc production process at an accelerator, allowing its use for preclinical and clinical PET imaging.

(44)CaCO3 targets were prepared and irradiated with protons (~11 MeV) at a beam current of 50 μA for 90 min. (44)Sc was separated from its target material using DGA extraction resin and concentrated using SCX cation exchange resin. Radiolabeling experiments at activities up to 500 MBq and stability tests were performed with DOTANOC by investigating different scavengers, including gentisic acid. Dynamic PET of an AR42J tumor-bearing mouse was performed after injection of (44)Sc-DOTANOC.

The optimized chemical separation method yielded up to 2 GBq (44)Sc of high radionuclidic purity. In the presence of gentisic acid, radiolabeling of (44)Sc with DOTANOC was achieved with a radiochemical yield of ~99% at high specific activity (10 MBq/nmol) and quantities which would allow clinical application. The dynamic PET images visualized increasing uptake of (44)Sc-DOTANOC into AR42J tumors and excretion of radioactivity through the kidneys of the investigated mouse.

The concept "from-bench-to-bedside" was clearly demonstrated in this extended study using cyclotron-produced (44)Sc. Sufficiently high activities of (44)Sc of excellent radionuclidic purity are obtainable for clinical application, by irradiation of enriched calcium at a cyclotron. This work demonstrates a promising basis for introducing (44)Sc to clinical routine of nuclear imaging using PET.