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Biomedical subjects

J Booij

Publications and source records attributed to J Booij.

54 records · Page 3Linked to original sources
PubMed1997

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.

Adult↗
PubMed1997

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

In vivo studies using single-photon emission tomography (SPET) and positron emission tomography have shown an age-related decline in the number of striatal dopamine transporters in healthy subjects. We examined ten healthy subjects and 33 de novo patients with Parkinson's disease (PD) using [123I]2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([123I]beta-CIT) SPET. A clear age-related loss of dopamine transporters was found in the healthy subjects. In the PD group, controlling for the contribution of disease severity, we found a small (compared with controls) but significant decrease with aging, though only in the ipsilateral regions. This aging effect was especially pronounced in younger patients. We conclude that the use of age-correct SPET data in PD, based on studies with healthy subjects, may lead to an under- or an overestimation of the striatal binding measures.

Adult↗
PubMed1997

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 Parkinson's disease (PD) has been accurately assessed in vivo by single-photon emission tomography (SPET) studies using [123I]beta-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]beta-CIT, which is not convenient for routine out-patient evaluations. Recently, a new ligand, N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(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]beta-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]beta-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]beta-CIT for the assessment of the dopaminergic deficit in PD. The faster kinetics of [123I]FP-CIT are a clear advantage.

Brain↗
PubMed1997

[123I]FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson's disease.

OBJECTIVES: The main neuropathological feature in Parkinson's disease is a severe degeneration of the dopaminergic neurons in the substantia nigra resulting in a loss of dopamine (DA) transporters in the striatum. [123I]beta-CIT single photon emission computed tomography (SPECT) studies have demonstrated this loss of striatal DA transporter content in Parkinson's disease in vivo. However, studies with this radioligand also showed that an adequate imaging of the striatal DA transporter content could only be performed on the day after the injection of radioligand, which is not convenient for outpatient evaluations. Recently, a new radioligand [123I]FP-CIT, with faster kinetics than beta-CIT, became available for imaging of the DA transporter with SPECT, and the applicability of this ligand was tested in patients with early and advanced Parkinson's disease, using a one day protocol. METHODS: [123I]FP-CIT SPECT was performed in six patients with early and 12 patients with advanced Parkinson's disease, and in six age matched healthy volunteers. RESULTS: Compared with an age matched control group striatal [123I]FP-CIT uptake in patients with Parkinson's disease was decreased, and this result was measurable three hours after injection of the radioligand. In the Parkinson's disease group the uptake in the putamen was reduced more than in the caudate nucleus. The contralateral striatal uptake of [123I]FP-CIT was significantly lower than the ipsilateral striatal uptake in the Parkinson's disease group. Specific to non-specific striatal uptake ratios correlated with the Hoehn and Yahr stage. A subgroup of patients with early Parkinson's disease also showed significantly lower uptake in the putamen and lower putamen:caudate ratios than controls. CONCLUSION: [123I]FP-CIT SPECT allows a significant discrimination between patients with Parkinson's disease and age matched controls with a one day protocol, which will be to great advantage in outpatient evaluations.

Adult↗
PubMed1996

In vitro and in vivo characterization of newly developed iodinated 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]piperazine derivatives in rats: limited value as dopamine transporter SPECT ligands.

A series of 1-{2-[bis(4-fluorophenyl)methoxy]ethyl}piperazines (CYD1, 2, 3, 5) with a 4-substituent incorporating a 1-hydroxy-3-iodo-2-propenyl moiety, except CYD2 which lacks the hydroxy, was synthesized as potential in vivo imaging ligands for the dopamine transporter. For two of the piperazine derivatives (CYD3 and 5), possible stereoselectivity was considered as well (both E- and Z-form). Their in vitro potency for inhibition of [3H]dopamine uptake in rat striatal synaptosomes was 10-fold lower than that of GBR 12,909 used as a reference. The highest Ki values were 137 and 101 nM for CYD1E and CYD3E, respectively. Inhibition potency was higher for the E- than for the Z-isomers. In vivo distribution of radioactivity in rats injected with the 123I-labeled CYDs showed preferred striatal uptake for CYD1E and CYD3E as compared to the cerebellum and occipital cortex. Although the E-isomer of CYD3 showed the best in vitro and in vivo binding characteristics, its striatal uptake ratios (maximal value: 2.7 for striatum-to-cerebellum at 4 h p.i.) are too low to consider application in human Single Photon Emission Computed Tomography studies.

Animals↗
PubMed1995

Evaluation of [123I] beta-CIT binding with SPECT in controls, early and late Parkinson's disease.

The main neuropathological feature in Parkinson's disease (PD) is a severe degeneration of the dopaminergic neurons in the substantia nigra resulting in a loss of dopamine in the striatum. Recently, a new radioligand (beta-CIT) for single photon emission computed tomography (SPECT) became available for in vivo imaging of the dopamine transporter on nerve endings of dopaminergic neurons in the striatum. The present results demonstrate that [123I]-beta-CIT SPECT allows a discrimination between early and late PD patients. In our opinion, these preliminary data suggest that [123I]-beta-CIT SPECT should be used from now on in longitudinal studies (such as the DATATOP study) in which the effects of (putative) neuroprotective interventions in PD are monitored.

Adult↗
PubMed1992

The anti-parkinsonian drug amantadine inhibits the N-methyl-D-aspartic acid-evoked release of acetylcholine from rat neostriatum in a non-competitive way.

The anti-viral drug amantadine is used in the treatment of Parkinson's disease without the drug having a well established mechanism of action. Amantadine is reported to displace the non-competitive NMDA receptor antagonist MK-801 from its binding site in the central nervous system. We show that amantadine inhibits, in a non-competitive way, the NMDA receptor-mediated stimulation of acetylcholine release from rat neostriatum in vitro in 'therapeutic' (i.e. low micromolar range) concentrations. Moreover, contrary to previous reports, amantadine, in this concentration range, did not affect the in vitro release of dopamine from neostriatal tissue.

Acetylcholine↗
PubMed1992

Amantadine as N-methyl-D-aspartic acid receptor antagonist: new possibilities for therapeutic applications?

The N-methyl-D-aspartic acid (NMDA) receptor is an intriguing target for the development of drugs with anti-Parkinsonian activity as well as with protective actions against degenerative processes induced by brain ischemia. Amantadine is used in the treatment of Parkinson's disease without a well established mechanism of action. We show here that amantadine inhibits, in a non-competitive way, the NMDA receptor-mediated stimulation of acetylcholine release from rat neostriatum in vitro in "therapeutic" (i.e., low micromolar) concentrations. This indicates that amantadine might exert its anti-Parkinsonian effect via blockade of NMDA receptors. Sustained stimulation of NMDA receptors induces so-called excitotoxicity. Recently, it was demonstrated that amantadine is able to inhibit NMDA induced cell death in a neuronal culture. On the basis of these findings it seems worth investigating if amantadine is also able to protect against neurodegenerative processes caused by brain ischemia in vivo.

Acetylcholine↗
PubMedDate not supplied

MDMA ("Ecstasy") and its association with cerebrovascular accidents: preliminary findings.

BACKGROUND AND PURPOSE: Abuse of the popular recreational drug "Ecstasy" (MDMA) has been linked to the occurrence of cerebrovascular accidents. It is known that MDMA alters brain serotonin (5-HT) concentrations and that brain postsynaptic 5-HT(2) receptors play a role in the regulation of brain microvasculature. Therefore, we used brain imaging to find out whether MDMA use predisposes one to cerebrovascular accidents by altering brain 5-HT neurotransmission. METHODS: The effects of MDMA use on brain cortical 5-HT(2A) receptor densities were studied using [(123)I]R91150 single-photon emission CT in 10 abstinent recent MDMA users, five former MDMA users, and 10 healthy control subjects. Furthermore, to examine whether changes in brain 5-HT(2A) receptor densities are associated with alterations in blood vessel volumes, we calculated relative cerebral blood volume maps from dynamic MR imaging sets in five MDMA users and six healthy control subjects. RESULTS: An analysis of variance revealed that mean cortical [(123)I]R91150 binding ratios were significantly lower in recent MDMA users than in former MDMA users and control subjects. This finding suggests down-regulation of 5-HT(2) receptors caused by MDMA-induced 5-HT release. Furthermore, in MDMA users, low cortical 5-HT(2) receptor densities were significantly associated with low cerebral blood vessel volumes (implicating vasoconstriction) and high cortical 5-HT(2) receptor densities with high cerebral blood vessel volumes (implicating vasodilatation) in specific brain regions. CONCLUSION: These findings suggest a relationship between the serotonergic system and an altered regulation of 5-HT(2) receptors in human MDMA users. MDMA users may therefore be at risk for cerebrovascular accidents resulting from alterations in the 5-HT neurotransmission system.

Adult↗