Differential kinetics of [123I]?-CIT binding to dopamine and serotonin transporters

Fujita, Masahiro; Takatoku, Keizo; Matoba, Yoshinori; Nishiura, Masaru; Kobayashi, Keiko; Ito, Osamu

doi:10.1007/bf01247372

Cited by 29 publications

(22 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another possibility is that the lower observed BP derives from the model used to estimate kinetic parameters. However, we calculated the estimated kinetics of [ 123 I]␤-CIT and [ 123 I]nor-␤-CIT with the model described by Fujita et al (1996). By using this model, we found similar kinetics of [ 123 I]␤-CIT binding in rat brain as reported by Fujita, which give support to the observed kinetic characteristics of [ 123 I]nor-␤-CIT.…”

Section: Discussionsupporting

confidence: 85%

Comparative in vivo study of iodine-123-labeled ?-cit and nor-?-cit binding to serotonin transporters in rat brain

Reneman

Booij

Lavalaye

et al. 1999

Synapse

View full text Add to dashboard Cite

Both iodine-123-labeled beta-CIT (2beta-carbomethoxy-3beta-(4-iodophenyl)tropane) and nor-beta-CIT (2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane) have shown to be suitable radioligands for imaging serotonin (5-HT) transporters. [(123)I]nor-beta-CIT has the highest in vitro affinity for 5-HT transporters among beta-CIT analogs reported so far. However, no direct comparison-studies of these two radiotracers as to their in vivo binding to 5-HT transporters have been reported so far. Therefore, it is still unclear which of the two radiotracers is more suitable for single photon emission computed tomography (SPECT) imaging of 5-HT transporters. The purpose of this study was to compare directly in a controlled design the in vivo [(123)I]beta-CIT and [(123)I]nor-beta-CIT binding to 5-HT transporters under the same conditions in rats with the focus on brain kinetic characteristics by means of a two-compartment analysis. We observed that [(123)I]beta-CIT has a higher binding potential and faster kinetics for 5-HT transporters than [(123)I]nor-beta-CIT, suggesting that [(123)I]beta-CIT may be a more suitable radioligand than [(123)I]nor-beta-CIT for imaging 5-HT transporters with SPECT.

show abstract

Section: Discussionsupporting

confidence: 85%

Comparative in vivo study of iodine-123-labeled ?-cit and nor-?-cit binding to serotonin transporters in rat brain

Reneman

Booij

Lavalaye

et al. 1999

Synapse

View full text Add to dashboard Cite

show abstract

“…21,23 In the hypothalamic/midbrain area, including raphe nuclei, ventral tegmental area, substantia nigra and the colliculi containing mainly serotonin transporters, [ 123 I]␤-CIT uptake reaches its highest value at 1-2 h after the injection. Thalamic activity (serotonin transporters) peaks at 4 h after the injection 24,25 correspondingly. Since previous studies have not revealed significant changes in blood flow either in the hypothalamus/midbrain area or in the thalamus in depressive states 52 ]␤-CIT in prefrontal cortex is low and rather within PET than SPET resolution.…”

Section: Molecular Psychiatrymentioning

confidence: 99%

“…22 This ratio can be used as an estimate of binding potential since the state of equilibrium has been documented to exist in the striatal and occipital areas at 24 h after the injection. Based on the findings of serotonin transporter binding kinetics, 21,[23][24][25][26] the following ratios at 1, 4 and 24 h after the injection were used for semiquantification of the serotonin transporters: HMB/OWM, Th/OWM and PF/OWM, the optimal imaging time in hypothalamic/midbrain area being 1 h, and in thalamus 4 h after the injection. 25,26 …”

Section: Spet Imagingmentioning

confidence: 99%

Elevated hypothalamic/midbrain serotonin (monoamine) transporter availability in depressive drug-naive children and adolescents

et al. 2000

View full text Add to dashboard Cite

Cumulative data suggest depression in adulthood being connected to reduced availability of brain serotonin while the role of dopamine remains less specific. Prospective studies have shown a continuity of depressive episodes from childhood to adulthood, combined with poor social function and excess mortality. The object of this study was to examine whether alterations in brain serotonin and/or dopamine transporter levels are already present in depressive children and adolescents. We examined 41 drug-naive patients (aged 7-17) by single photon emission tomography (SPET) using iodine-123-labelled 2␤-carbomethoxy-3␤(iodophenyl) tropane [ 123 I]␤-CIT as a tracer for monoamine transporters. In addition to the ordinary clinical examination, the patients were given a structured interview and information was gathered from teachers and parents with questionnaires. The diagnoses were established by consensus evaluation between three child psychiatrists. To test the serotonin hypothesis and the dopamine hypothesis regarding depression in children and adolescents, the series was divided into groups with depression present (31) and no depression present (10). In this study, the depressive child and adolescent patients had significantly higher serotonin transporter availability (P Ͻ 0.02) in the hypothalamic/midbrain area. Age did not correlate to the hypothalamic/midbrain serotonin transporter binding ratio. No significant difference in dopamine transporter availability in striatum was found between the depressive and the nondepressive children and adolescents. Molecular Psychiatry (2000) 5, 514-522.

show abstract

“…In the present study, we used the radioactivity in the cerebellum as the input function for the kinetic analysis or the nonspecific binding of [ 123 I]␤-CIT in brain, as previously reported (Fujita et al, 1996(Fujita et al, , 1997. No significant changes in radioactivity in the cerebellum were observed in the MK-801 pretreated rats (Fig.…”

Section: Discussionmentioning

confidence: 90%

Enhancement of in vivo binding of [123I]?-CIT by MK-801 in rat brain

Nakano

Takatoku

Matoba

et al. 1998

Synapse

Self Cite

View full text Add to dashboard Cite

The effects of MK-801, a noncompetitive NMDA receptor antagonist, on in vivo and in vitro binding of radioactive iodine ([123I] or [125I]) labeled beta-CIT [RTI-55, 3beta-(4-iodophenyl)tropane-2beta-carboxylic acid methyl ester] were investigated in rat brain. In the in vitro binding study, 10 pM of [125I]beta-CIT was incubated with either 0.03 microM or 3 microM of MK-801 at 24 degrees C for 60 min. In vitro, no alterations in [125I]beta-CIT binding in any region of rat brain slices were detected after addition of MK-801. In the in vivo binding study, [123I]beta-CIT was intravenously injected into rats 30 min after intraperitoneal injection of 0.03-1 mg/kg of MK-801. The in vivo [123I]beta-CIT binding in the striatum, frontal cortex, occipital cortex, hypothalamus, and thalamus was significantly increased by pretreatment with 1 mg/kg of MK-801. Kinetic analysis using the cerebellum as a reference region revealed that the increases in in vivo [123I]beta-CIT binding induced by MK-801 were mainly due to increases in both input rate constant k3 and output rate constant k4. The results of this study indicate that the glutamatergic system, including NMDA receptor, plays an important role in regulating neurotransmission in the dopaminergic or serotonergic systems in intact brain.

show abstract

Differential kinetics of [123I]?-CIT binding to dopamine and serotonin transporters

Cited by 29 publications

References 35 publications

Comparative in vivo study of iodine-123-labeled ?-cit and nor-?-cit binding to serotonin transporters in rat brain

Comparative in vivo study of iodine-123-labeled ?-cit and nor-?-cit binding to serotonin transporters in rat brain

Elevated hypothalamic/midbrain serotonin (monoamine) transporter availability in depressive drug-naive children and adolescents

Enhancement of in vivo binding of [123I]?-CIT by MK-801 in rat brain

Contact Info

Product

Resources

About