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Open Access Highly Accessed Original research

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

Miia Pitkonen1, Eero Hippeläinen25, Mari Raki1, Jaan-Olle Andressoo3, Arto Urtti1, Pekka T Männistö4, Sauli Savolainen5, Mart Saarma3 and Kim Bergström1*

Author Affiliations

1 Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5E), Helsinki, 00014, Finland

2 HUS Medical Imaging Center, Helsinki University Central Hospital, Helsinki, 00290, Finland

3 Institute of Biotechnology, University of Helsinki, Helsinki, 00014, Finland

4 Division of Pharmacology and Toxicology, Faculty of Pharmacy, University of Helsinki, Helsinki, 00014, Finland

5 Department of Physics, University of Helsinki, Helsinki, 00014, Finland

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EJNMMI Research 2012, 2:55  doi:10.1186/2191-219X-2-55

Published: 29 September 2012

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords:
SPECT/CT; Dopamine transporters; 123I β-CIT; Tracer kinetics