Cyclotron production of 44Sc: From bench to bedside

Abstract

Introduction44Sc, a PET radionuclide, has promising decay characteristics (T1/2=3.97h, Eβ+av=632keV) for nuclear imaging and is an attractive alternative to the short-lived 68Ga (T1/2=68min, Eβ+av=830keV). The aim of this study was the optimization of the 44Sc production process at an accelerator, allowing its use for preclinical and clinical PET imaging. Methods44CaCO3 targets were prepared and irradiated with protons (~11MeV) at a beam current of 50μA for 90min. 44Sc was separated from its target material using DGA extraction resin and concentrated using SCX cation exchange resin. Radiolabeling experiments at activities up to 500MBq 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 44Sc-DOTANOC. ResultsThe optimized chemical separation method yielded up to 2GBq 44Sc of high radionuclidic purity. In the presence of gentisic acid, radiolabeling of 44Sc with DOTANOC was achieved with a radiochemical yield of ~99% at high specific activity (10MBq/nmol) and quantities which would allow clinical application. The dynamic PET images visualized increasing uptake of 44Sc-DOTANOC into AR42J tumors and excretion of radioactivity through the kidneys of the investigated mouse. ConclusionsThe concept “from-bench-to-bedside” was clearly demonstrated in this extended study using cyclotron-produced 44Sc. Sufficiently high activities of 44Sc 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 44Sc to clinical routine of nuclear imaging using PET.