Single photon emission computed tomographic imaging demonstrates loss of striatal dopamine transporters in Parkinson disease.

Abstract

ABSTRACT[123I][(lR)-2(3-carbomethoxy-3fl-(4-iodophenyl)tropane] ([123'IJ-CIT) labels dopamine transporters and is, therefore, a marker of neurons that degenerate in Parkinson disease. Single photon emission computed tomography imaging with [123I]P-CIT showed that radioactivity in striatal regions in healthy subjects increased during a 2-day imaging study, whereas that in Parkinsonian patients peaked earlier at reduced levels relative to healthy subjects. Kinetic analyses of radioactivity in plasma and brain suggest that this decrease was due to an =65% loss of target sites in patients compared with healthy subjects; greater losses occurred in putamen than in caudate. AU patients showed lateralized differences in striatal uptake, with greater losses in the striatum contralateral to the side of the body with initial symptoms. These preliminary results suggest that [123'IJ-CIT is a marker for the loss of striatal dopamine terminals in patients with Parkinson disease. Single photon emission computed tomographic imaging with [123'I-CIT may be useful for early diagnosis of the disorder, for monitoring the progression of the disease, and for distinguishing the idiopathic disorder from other Parkinsonian syndromes with more widespread pathology.Parkinson disease is a progressive, disabling neurodegenerative disorder characterized clinically by tremor at rest, bradykinesia, rigidity, and postural instability. The disorder is characterized pathologically by the degeneration of dopaminergic neurons in the substantia nigra, resulting in an 80-99% reduction in striatal dopamine concentrations (1) and a corresponding loss of dopamine transporters (2). Dopamine replacement with either the precursor L-dopa (L-dihydroxyphenylalanine) or direct dopamine-receptor agonists effectively reverses the motor deficits of the disease early in its course. However, as the disease progresses, patients develop disabilities from a number of drug-induced side effects, progression of motor dysfunction (due to continued degeneration of dopamine nerve terminals), and an array of nonmotor, non-dopamine responsive symptoms. Therefore, recent research has focused on developing therapeutic strategies to prevent progression of disease by halting neuronal death and/or restoring neuronal function. Several carbomethoxy-33-(4-iodophenyl)tropane ([123I]3-CIT) (4)[also designated RTI-55 (5)], which labels the dopamine transporter. This protein is located in the presynaptic membrane and transports dopamine from the synapse back into the terminal. That is, [123I]f3-CIT labels sites located on the terminals of dopamine neuronal projections from the substantia nigra to the striatum and may, therefore, provide a measure of dopamine terminal innervation. METHODS SPECT imaging of [123I]3-CIT was done in five patients withidiopathic Parkinson disease and five sex-matched healthy subjects; both groups had a similar mean age. All patients had symptoms that were responsive to L-dopa and had at least three of the following symptoms: resting tremor, bradykinesia, rigi...

Dopamine Transporter in vitro Binding and in vivo Imaging in the Brain

“…It has been used in several studies to observe the changes in the density of dopamine transporter in human brain (Innis et al 1993;Brücke et al 1993;Kuikka et al 1993;Tiihonen et al 1995). b-CIT also MiniReview has affinity to the serotonin transporter (Boja et al 1994), which makes the interpretation of the analysis of radioactivity distribution difficult in brain areas possessing high density of both 5-HT-and dopamine transporters.…”

Serotonin and Dopamine Transporter Availabilities Correlate with the Loudness Dependence of Auditory Evoked Potentials in Patients with Obsessive-Compulsive Disorder

“…[ 123 I]-2b-carbomethoxy-3b-(4-iodophenyl)tropane ([ 123 I]b-CIT) is a radiotracer with high affinity to monoamine transporters (Innis et al, 1991;Boja et al, 1992) and thus can be used to visualize the central serotonin (SERT) and dopamine transporters (DAT) of the human brain in vivo with single photon emission computed tomography (SPECT) (Innis et al, 1993;Kuikka et al, 1993;Brücke et al, 1993;Pirker et al, 2000). b-CIT has been shown to accumulate in distinct brain areas, primarily in striatal, diencephalic, midbrain, and brainstem regions (Innis et al, 1991;Laruelle et al, 1993).…”

[123I]β-CIT single-photon emission tomography in Parkinson's disease reveals a smaller decline in dopamine transporters with age than in controls

“…In SPET studies using [ 123 I]2β-carbomethoxy-3β-(4-iodophenyl)tropane ([ 123 I]β-CIT), which has been shown to be sensitive to dopaminergic presynaptic degeneration [4], Van Dyck et al confirmed in 28 healthy subjects the post-mortem reports on DA transporter loss with increasing age [5].…”