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

Nicholas P van der Meulen; Maruta Bunka; Katharina A Domnanich; Cristina Müller; Stephanie Haller; Christiaan Vermeulen; Andreas Türler; Roger Schibli

doi:10.1016/j.nucmedbio.2015.05.005

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

Nucl Med Biol. 2015 Sep;42(9):745-51. doi: 10.1016/j.nucmedbio.2015.05.005. Epub 2015 May 30.

Authors

Nicholas P van der Meulen¹, Maruta Bunka², Katharina A Domnanich³, Cristina Müller⁴, Stephanie Haller⁴, Christiaan Vermeulen⁴, Andreas Türler³, Roger Schibli⁵

Affiliations

¹ 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.
² Laboratory of Radiochemistry and Environmental Chemistry, Department of Chemistry and Biochemistry University of Bern, Bern, Switzerland.
³ 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.
⁴ Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland.
⁵ Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen-PSI, Switzerland; Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.

PMID: 26093495
DOI: 10.1016/j.nucmedbio.2015.05.005

Abstract

Introduction: (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.

Keywords: (44)Ca target; (44)Sc; Cyclotron; DOTANOC; PET.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Algorithms*
Computer Graphics
Computer Simulation
Image Enhancement / methods
Image Interpretation, Computer-Assisted / methods*
Imaging, Three-Dimensional / methods*
Information Storage and Retrieval / methods*
Machine Learning
Models, Biological
Models, Statistical
Multimodal Imaging / methods*
Numerical Analysis, Computer-Assisted
Pattern Recognition, Automated / methods*
Reproducibility of Results
Sensitivity and Specificity
Signal Processing, Computer-Assisted
Subtraction Technique*
User-Computer Interface