E. A. Van Royen

Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group.

To evaluate whether visual assessment of [123I]‐FP‐CIT (DaTSCAN , Nycomed Amersham, plc) single photon emission computerized tomography (SPECT) images can differentiate between parkinsonism and essential tremor (ET).

Effect of age and gender on dopamine transporter imaging with [123I]FP-CIT SPET in healthy volunteers.

Abstract.Dopamine transporter imaging is a valuable tool to investigate the integrity of the dopaminergic neurons. To date, several reports have shown an age-associated decline in dopamine transporters in healthy volunteers. Although animal studies suggest an effect of gender on dopamine transporter density, this gender effect has not yet been confirmed in human studies. To study the influence of age and gender on dopamine transporter imaging in healthy volunteers, we performed single-photon emission tomography imaging with [123I]FP-CIT to quantify dopamine transporters. Forty-five healthy volunteers (23 males and 22 females) were included, ranging in age from 18 to 83 years. SPET imaging was performed 3 h after injection of ±110 MBq [123I]FP-CIT. An operator-independent volume of interest analysis was used for quantification of [123I]FP-CIT binding in the striatum. The ratio of specific striatal to non-specific [123I]FP-CIT binding was found to decrease significantly with age. Moreover, we found a high variance in [123I]FP-CIT binding in young adults. Finally, females were found to have significantly higher [123I]FP-CIT binding ratios than males. This effect of gender on [123I]FP-CIT binding ratios was not related to age. The results of this study are consistent with findings from previous studies, which showed that dopamine transporter density declines with age. The intriguing finding of a higher dopamine transporter density in females than in males is in line with findings from animal studies.

Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism

Abstract. Parkinsonism is a feature of a number of neurodegenerative diseases, including Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy. The results of post-mortem studies point to dysfunction of the dopaminergic neurotransmitter system in patients with parkinsonism. Nowadays, by using single-photon emission tomography (SPET) and positron emission tomography (PET) it is possible to visualise both the nigrostriatal dopaminergic neurons and the striatal dopamine D2 receptors in vivo. Consequently, SPET and PET imaging of elements of the dopaminergic system can play an important role in the diagnosis of several parkinsonian syndromes. This review concentrates on findings of SPET and PET studies of the dopaminergic neurotransmitter system in various parkinsonian syndromes.

Drug-naive patients with Parkinson’s disease in Hoehn and Yahr stages I and II show a bilateral decrease in striatal dopamine transporters as revealed by [123I]β-CIT SPECT

Abstract Ten healthy subjects and 16 patients with early Parkinson’s disease (PD) were examined with single photon emission computed tomography (SPECT) and [123I]β-CIT, a ligand for the dopamine (DA) transporter. Only drug-naive patients were examined since the expression of and binding to DA transporters may be influenced by dopaminergic medication. The main finding was a significant reduction in [123I]β-CIT binding in the ipsi- and contralateral striatal regions, especially in the putamen, which showed a mean reduction of 65% of the control mean. Discriminant function analysis of the putaminal [123I]β-CIT binding measures classified 100% of the cases in the correct group. Disease severity correlated negatively and highly significantly with the binding measures. Tremor ratings did not correlate with the SPECT measures, whereas rigidity, and to a lesser extent bradykinesia, did. Patients with unilateral PD showed a bilateral loss of striatal DA transporters. Our findings indicate that with [123I]β-CIT SPECT it is possible to diagnose PD in subjects with very mild symptoms and signs. Moreover, finding a bilateral loss of striatal DA transporters in patients with unilateral PD also suggests that it may be possible to identify subjects in the preclinical phase of the disease.

The Value of Radiographs and Bone Scintigraphy in Suspected Scaphoid Fracture A Statistical Analysis

The role of radiography and bone scintigraphy in the diagnostic management of suspected scaphoid fracture is controversial. Two strategies were compared for patients with initial negative radiographs: repeated radiography versus selective bone scintigraphy. Using the known positive predictive value of scintigraphy, the sensitivity and specificity of both diagnostic strategies were evaluated in a series of 78 consecutive patients. The kappa value for initial radiographs was 0.76 but decreased to 0.5 for follow-up radiographs. Similarly, sensitivity decreased from 64% to 30% in follow-up radiographs. Specificity of the bone scan was 98%. The best diagnostic strategy in the management of clinically suspected scaphoid fractures consists of initial radiography followed by bone scintigraphy in patients with negative radiographs.

Practical benefit of [123I]FP-CIT SPET in the demonstration of the dopaminergic deficit in Parkinson's disease

Loss of striatal dopamine (DA) transporters in Parkinsons disease (PD) has been accurately assessed in vivo by single-photon emission tomography (SPET) studies using [123I]β-CIT. However, these studies have also shown that adequate imaging of the striatal DA transporter content can be performed only 20–30 h following the injection of [123I]β-CIT, which is not convenient for routine out-patient evaluations. Recently, a new ligand,N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)tropane (FP-CIT), became available for in vivo imaging of the DA transporter. The faster kinetics of [123I]FP-CIT have been shown to allow adequate acquisition as early as 3 h following injection. In the present study, loss of striatal DA transporters in five non-medicated PD patients was assessed on two consecutive SPET scans, one with [123I]β-CIT (24 h following injection) and one with [123I]FP-CIT (3 h following injection). The ratios of specific to non-specific [123I]FP-CIT uptake in the caudate nucleus and putamen were consistently 2.5-fold lower than those of [123I]β-CIT. However, when the uptake ratio of both ligands in these brain regions of patients was expressed as a percentage of the uptake ratio found in healthy controls, both the decrease and the variation of the data were similar. It is concluded on the basis of these findings that [123I]FP-CIT seems as good as [123I]β-CIT for the assessment of the dopaminergic deficit in PD. The faster kinetics of [123I]FP-CIT are a clear advantage.

[123I]FP-CIT binds to the dopamine transporter as assessed by biodistribution studies in rats and SPECT studies in MPTP-lesioned monkeys

[123I]FP‐CIT (N‐ω‐fluoropropyl‐2β‐carbomethoxy‐3β‐{4‐iodophenyl}tropane), a radioiodinated cocaine analogue, was evaluated as an agent for the in vivo labeling of dopamine (DA) transporters by biodistribution studies in rats and by single photon emission computed tomography (SPECT) studies in unilateral 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)–lesioned monkeys. In rats, intravenous injection of [123I]FP‐CIT resulted in high accumulation of radioactivity in the striatum. Less pronounced uptake was seen in brain areas with high densities of serotonergic uptake sites. While striatal uptake of radioactivity after injection of [123I]FP‐CIT was displaced significantly by GBR12,909 but not by fluvoxamine, the opposite was observed in brain areas known to be rich of serotonin transporters. Monkeys which were unilaterally treated with neurotoxic doses of MPTP showed severe loss of striatal [123I]FP‐CIT uptake at the side of treatment. The results of this study indicate that [123I]FP‐CIT, although not being a selective radioligand, binds specifically to the striatal DA transporter in vivo and thus suggest that [123I]FP‐CIT promises to be a suitable radioligand for SPECT imaging of DA transporters in humans. Synapse 27:183–190, 1997.

Octreotide‐scintigraphy is a disease‐activity parameter in Graves' ophthalmopathy

It is thought that immunosuppressive treatment of Graves ophthalmopathy should be restricted to patients with active eye disease, but assessing disease activity is difficult. Octreotide scintigraphy has been claimed to differentiate active from inactive disease. Here we study the intraobserver variability and diagnostic accuracy of the quantitative measurement of orbital octreotide uptake.

In vivo characterisation of 3-iodo-6-methoxybenzamide 123I in humans.

Abstract3-Iodo-6-methoxybenzamide (123I-IBZM), a new Dopamine D2 receptor ligand, was used in conjunction with SME 810 brain tomography to study six subjects (one normal volunteer, four schizophrenics and one DAT patient). Initial Dynamic SPET was followed by multislice SPET. High-resolution images of the D2 receptor distribution in the basal ganglia were obtained. The specific binding in D2 receptors of the basal ganglia is highest from 2–4 h p.i. Patients on anti-psychotic drugs showed significantly lower specific binding. Dopamine D2 brain receptor availability in man may now be studied with SPET. Continuous data acquisition with single slice tomography is particularly important in the study of this type of radiotracers.

Assessment of endogenous dopamine release by methylphenidate challenge using iodine-123 iodobenzamide single-photon emission tomography

This double-blind, placebo-controlled study assessed pharmacologically induced endogenous dopamine (DA) release in healthy male volunteers (n=12). Changes in endogenous DA release after injection of the psychostimulant drug methylphenidate were evaluated by single-photon emission tomography (SPET) and constant infusion of iodine-123 iodobenzamide ([123I]IBZM), a D2 receptor radioligand that is sensitive to endogenous DA release. Methylphenidate induced displacement of striatal [123I]IBZM binding, resulting in a significantly decrease in the specific to non-specific [123I]IBZM uptake ratio (average: 8.6%) in comparison with placebo (average: −1.9%). Moreover, injection of methylphenidate induced significant behavioural responses on the following items: excitement, anxiety, tension, and mannerisms and posturing. The results of this study demonstrate the feasibility of using constant infusion of [123I]IBZM and SPET imaging to measure endogenous DA release after methylphenidate challenge and to investigate neurochemical aspects of behaviour.