Advanced brain dopamine transporter imaging in mice using small-animal SPECT/CT

Springer Science and Business Media LLC - 2012
Miia Pitkonen1, Eero Hippeläinen2,3, Mari Raki1, Jaan-Olle Andressoo4, Arto Urtti1, Pekka T Männistö5, Sauli Savolainen3, Mart Saarma4, Kim Bergström1
1Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
2HUS Medical Imaging Center, Helsinki University Central Hospital, Helsinki, Finland
3Department of Physics, University of Helsinki, Helsinki, Finland
4Institute of Biotechnology, University of Helsinki, Helsinki, Finland
5Division of Pharmacology and Toxicology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland

Tóm tắt

Iodine-123-β-CIT, a single-photon emission computed tomography (SPECT) ligand for dopamine transporters (DATs), has been used for in vivo studies in humans, monkeys, and rats but has not yet been used extensively in mice. To validate the imaging and analysis methods for preclinical DAT imaging, wild-type healthy mice were scanned using 123I-β-CIT. The pharmacokinetics and reliability of 123I-β-CIT in mice (n = 8) were studied with a multipinhole SPECT/CT camera after intravenous injection of 123I-β-CIT (38 ± 3 MBq). Kinetic imaging of three mice was continued for 7 h postinjection to obtain the time-activity curves in the striatum and cerebellum volumes. Five mice had repeated measures 4 h post-123I-β-CIT injection to provide an indication of test-retest reliability. The same five mice served as a basis for a healthy mean SPECT template. Specific binding of 123I-β-CIT within the mouse striatum could be clearly visualized with SPECT. The kinetics of 123I-β-CIT was similar to that in previously published autoradiography studies. Binding potential mean values of the test-retest studies were 6.6 ± 15.7% and 6.6 ± 4.6%, respectively, and the variability was 9%. The SPECT template was aggregated from the first and second imaging of the test-retest animals. No significant difference between the templates (P > 0.05) was found. From the test template, a striatal volume of 22.3 mm3 was defined. This study demonstrates that high-resolution SPECT/CT is capable of accurate, repeatable, and semiquantitative measurement of 123I-β-CIT DAT binding in the mouse brain. This methodology will enable further studies on DAT density and neuroprotective properties of drugs in mice.

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