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Imaging Serotonin and Dopamine Transporters with ¹²³I-ß-CIT SPECT: Binding Kinetics and Effects of Normal Aging

Departments of Neurology, Nuclear Medicine, and General Psychiatry, University of Vienna, Vienna
Forschungszentrum Seibersdorf, Seibersdorf, Vienna, Austria
Department of Neurology, Wilhelminenspital, Vienna, Austria

Correspondence: For correspondence or reprints contact: Walter Pirker, MD, Department of Neurology, University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria.

ABSTRACT

[¹²³I]ß-carbomethoxy-3-ß-(4-iodophenyl)-tropane (CIT) is a useful ligand for dopamine transporters (DATs) and serotonin transporters (5-HTTs). Previous SPECT studies have shown a state of sustained equilibrium in the striatum on day 2 after injection that allows quantification of striatal DATs using a simple ratio of specific-to-nondisplaceable binding. The aim of this study was to investigate the kinetics of [¹²³I]ß3-CIT uptake in the thalamus, hypothalamus, and midbrain, areas known to contain 5-HTTs in high densities. Methods: SPECT with a triple-head camera was performed on 16 healthy volunteers (13 women, 3 men; mean age [±SD], 32 ± 11 y) after intravenous bolus injection of 130 ± 20 MBq (3.5 ± 0.5 mCi) [¹²³I]ß-CIT. Two individuals were scanned 1, 2, 4, 7, 10, 13, 16, and 24 h after injection, and the remaining 24 were scanned 4, 7, 10, 20, and 24 h after injection. Values from 19 previously examined healthy volunteers (8 women, 11 men; mean age, 52 ± 20 y) were included in the analysis to study the age dependency of ß-CIT binding in striatal and 5-HTT-rich brain areas in a larger control sample. Results: Peak uptake 4 h after injection followed by stable uptake until 10 h and a slow decrease until 24 h, was observed in the thalamus-hypothalamus region. Activity in the midbrain-pons region peaked 2 h after injection. Because of a concomitant slow but steady decline of uptake in reference regions starting 4 h after injection, a higher stability of binding ratios for 5-HTT-rich brain areas was observed on day 2, suggesting that a state of transient equilibrium is reached between 20 and 24 h but that conditions are only close to transient equilibrium between 4 and 10 h after injection for 5-HTT-rich brain areas. In addition to an age-related decline of striatal [¹²³I]ß-CIT binding of 6.6% per decade, a significant age-associated decrease of ß-CIT binding of 3–4% per decade was found in 5-HTT-rich brain areas. The decline of ß-CIT binding in these regions may be explained, at least in part, by a loss of monoamine transporters with age but may also be related to age-associated morphologic changes. Conclusion: [¹²³I]ß-CIT appears to be a suitable ligand for imaging serotonin transporters with SPECT. However, careful age matching is warranted for [¹²³I]ß-CIT SPECT studies of 5-HTT changes in patients with neuropsychiatric disorders.

Key Words: serotonin transporter • [¹²³I]ß-CIT • SPECT • kinetics • age dependency

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