Imaging serotonin and dopamine transporters with I-123-beta-CIT SPECT: Binding kinetics and effects of normal aging

[I-123]beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane (CIT) is a useful li gand far dopamine transporters (DATs) and serotonin transporters (5-HTTs). Previous SPECT studies have shown a state of sustained equilibrium in the s triatum on day 2 after injection that allows quantification of striatal DAT s using a simple ratio of specific-fo-nondisplaceable binding;The aim of th is study was to investigate the kinetics of [I-123]beta-CIT uptake in the t halamus, hypothalamus, and midbrain, areas known to contain 5-HTTs in high densities. Methods: SPECT with a triple-head camera was performed on 16 hea lthy volunteers (13 women, 3 men; mean age [+/- SD], 32 +/- 11 y) after int ravenous bolus injection of 130 +/- 20 MBq (3.5 +/- 0.5 mCi) [I-123]beta-CI T. Two individuals were scanned, 2, 4, 7, 10, 13, 16, and 24 h after inject ion, and the remaining 14 were scanned 4, 7, 10, 20, and 24 h after injecti on. 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 depe ndency of P-GIT binding in striatal and 5-HTT-rich brain areas in a larger control sample. Results: Peak uptake 4 h after injection, followed by stabl e uptake until 10 h and a slow decrease until 24 h, was observed in the tha lamus-hypothalamus region;Activity in the midbrain-pens region peaked 2 h a fter injection. Because of a concomitant slow but steady decline of uptake in reference regions starting 4 h after injection, a higher stability of bi nding ratios for 5-HTT-rich brain areas was observed on day 2, suggesting t hat a state of transient equilibrium is reached between 20 and 24 h but tha t conditions are only close to transient equilibrium between 4 and 10 h aft er injection for 5-HTT-rich brain areas. In addition to an age-related decl ine of striatal [I-123]beta-CIT binding of 6.6% per decade, a significant a ge-associated decrease of P-GIT binding of 3-4% per decade was found in 5-H TT-rich brain areas. The decline of P-CIT binding in these regions may be e xplained, at least in part, by a loss of monoamine transporters with age bu t may also be related to age-associated morphologic changes. Conclusion: [I -123]beta-CIT CIT appears to be a suitable ligand for imaging serotonin tra nsporters with SPECT. However, careful age matching is warranted for [I-123 ]beta-CIT SPECT studies of 5-HTT changes in patients with neuropsychiatric disorders.