Cyclotron production of 44Sc: From bench to bedside

Introduction: Sc-44. a PET radionuclide, has promising decay characteristics (T-1/2 = 3.97 h, E beta(+)(av), = 632 key) for nuclear imaging and is an attractive alternative to the short-lived Ga-68 (T-1/2 = 68 mm, E beta(+)(av) = 830 key). The aim of this study was the optimization of the Sc-44 production process at an accelerator, allowing its use for pre-clinical and clinical PET imaging. Methods: (CaCO3)-Ca-44 targets were prepared and irradiated with protons (similar to 11 MeV) at a beam current of 50 mu A for 90 mm. Sc-44 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 Sc-44-DOTANOC Results: The optimized chemical separation method yielded up to 2 GBq Sc-44 of high radionuclidic purity. In the presence of gentisic acid, radiolabeling of Sc-44 with DOTANOC was achieved with a radiochemical yield of similar to 99% at high specific activity (10 MBq/nmol) and quantities which would allow clinical application. The dynamic PET images visualized increasing uptake of Sc-44-DOTANOC into AR42J tumors and excretion of radioactivity through the kidneys of the investigated mouse. Conclusions: The concept from-bench-to-bedside was clearly demonstrated in this extended study using cyclotron-produced Sc-44. Sufficiently high activities of Sc-44 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 Sc-44 to clinical routine of nuclear imaging using PET. (C) 2015 Elsevier Inc. All rights reserved.