title: Cyclotron production of (44)Sc: From bench to bedside.
abstract: BACKGROUND
  (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.
  
  
  METHODS
  (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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland; Laboratory of Radiochemistry and Environmental Chemistry, Paul Scherrer Institute, Villigen-PSI, Switzerland. Electronic address: nick.vandermeulen@psi.ch.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: van der Meulen
authors.affiliation: Laboratory of Radiochemistry and Environmental Chemistry, Department of Chemistry and Biochemistry University of Bern, Bern, Switzerland.
authors.forename: Maruta
authors.initials: M
authors.lastname: Bunka
authors.affiliation: Laboratory of Radiochemistry and Environmental Chemistry, Paul Scherrer Institute, Villigen-PSI, Switzerland; Laboratory of Radiochemistry and Environmental Chemistry, Department of Chemistry and Biochemistry University of Bern, Bern, Switzerland.
authors.forename: Katharina A
authors.initials: KA
authors.lastname: Domnanich
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland.
authors.forename: Cristina
authors.initials: C
authors.lastname: Müller
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Haller
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland.
authors.forename: Christiaan
authors.initials: C
authors.lastname: Vermeulen
authors.affiliation: Laboratory of Radiochemistry and Environmental Chemistry, Paul Scherrer Institute, Villigen-PSI, Switzerland; Laboratory of Radiochemistry and Environmental Chemistry, Department of Chemistry and Biochemistry University of Bern, Bern, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Türler
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland; Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: Schibli
mesh_terms: D000465:Algorithms; D003196:Computer Graphics; D003198:Computer Simulation; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D016247:Information Storage and Retrieval / Q000379:methods*; D000069550:Machine Learning; D008954:Models, Biological; D015233:Models, Statistical; D064847:Multimodal Imaging / Q000379:methods*; D009716:Numerical Analysis, Computer-Assisted; D010363:Pattern Recognition, Automated / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012815:Signal Processing, Computer-Assisted; D013382:Subtraction Technique; D014584:User-Computer Interface
keywords: (44)Ca target; (44)Sc; Cyclotron; DOTANOC; PET