[123I]-2.beta.-carbomethoxy-3.beta.-(4-iodophenyl)tropane: high-affinity SPECT (single photon emission computed tomography) radiotracer of monoamine reuptake sites in brain

Neumeyer, John L.; Wang, Shaoyin; Milius, Richard A.; Baldwin, Ronald M.; Zea‐Ponce, Yolanda; Hoffer, Paul B.; Sybirska, Elzbieta; Al-Tikriti, Mohammed S.; Charney, Dennis S.

doi:10.1021/jm00114a027

Cited by 231 publications

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“…The total density of co caine binding sites related to DA transporter sites in the caudate of primates was estimated as 340 nM with eH]cocaine (Madras et a!., 1989a), 459 nM with [ 3 H]CFT (Madras et a!., 1989b), and 478 nM with e 2 5 I]f3-CIT (Laruelle et a!., 1994c). Using the latter value, a BP of 462 would be compatible with an average affinity of 1.0 nM, a value in accordance with the in vitro IC 5 0 of e 2 5 I][3-CIT for the DA transporter (1.6 nM) measured in primate striatum (Neumeyer et aI., 1991).…”

Section: Discussionsupporting

confidence: 74%

“…A three-compartment kinetic analysis of day 1 data were performed using a three (k4 = 0)-and a four (k4 > O)-parameter model. The three-parameter 2[3-Carbomethoxy -3 [3-( 4-iodophenyl)tropane ([3-CIT; also referred to as RTI-55) is a potent cocaine analogue with a high affinity for the dopamine (DA) and serotonin (5-HT) transporters (Carroll et aI., 1991;Neumeyer et aI., 1991 Abbreviations used: AIC , Akaike's information criteria; BP, binding potential; I3-CIT, 213-carboxy methoxy-313-(4-iodophenyl)tropane; %cv , percentage coefficient of variation; DA, dopamine; 5-HT, 5-hydroxytryptamine; SPECT, single photon emission computed tomography. …”

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confidence: 99%

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Graphical, Kinetic, and Equilibrium Analyses of in vivo [¹²³I]β-CIT Binding to Dopamine Transporters in Healthy Human Subjects

Laruelle

Wallace

Seibyl

et al. 1994

J Cereb Blood Flow Metab

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Summary:The in vivo kinetics of the dopamine (DA) transporter probe 1 2 3 I-labeled 2r3-carboxymethoxy-3r3-(4-iodophenyl)tropane ([1 2 3 1]r3-CIT) in striatum was investi gated with single-photon emission computerized tomog raphy (SPECT) in five healthy human subjects. The aim of this study was to derive an adequate measure of the DA transporter density that would not be affected by re gional cerebral blood flow or peripheral clearance of the tracer. SPECT data were acquired on the day of injection (day 1) from 0 to 7 h and on the following day (day 2) from 19 to 25 h. Arterial sampling on day 1 was used to mea sure the input function. Graphical, kinetic, and equilib rium analyses were evaluated. Graphical analysis of day 1 data, with the assumption of negligible dissociation of the tracer-receptor complex (k4 = 0), was found to be blood flow-dependent. A three-compartment kinetic analysis of day 1 data were performed using a three (k4 = 0)-and a four (k4 > O)-parameter model. The three-parameter 2[3-Carbomethoxy -3 [3-( 4-iodophenyl)tropane ([3-CIT; also referred to as RTI-55) is a potent cocaine analogue with a high affinity for the dopamine (DA) and serotonin (5-HT) transporters (Carroll et aI., 1991;Neumeyer et aI., 1991 Abbreviations used: AIC , Akaike's information criteria; BP, binding potential; I3-CIT, 213-carboxy methoxy-313-(4-iodophenyl)tropane; %cv , percentage coefficient of variation; DA, dopamine; 5-HT, 5-hydroxytryptamine; SPECT, single photon emission computed tomography. 982model estimated the konBmax product at 0.886 ± 0.087 min -1 . The four-parameter model gave a binding poten tial (BP) of 476 ml g-l , a value consistent with in vitro measurements. The stability of the regional uptake on day 2 allowed direct measurement of the specific to nonspe cific equilibrium partition coefficient (V 3 " = k31k4 = 6.66 ± 1.54). Results of day 1 kinetic analysis and day 2 equi librium analysis were well correlated among subjects. Simulations indicated that the error associated with the day 2 equilibrium analysis was acceptable for plasma tracer terminal half-lives > 10 h. We propose the equilib rium analysis on day 2 as the method of choice for clinical studies since it does not require multiple scans or the measurement of the arterial plasma tracer concentrations.

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Section: Discussionsupporting

confidence: 74%

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confidence: 99%

Graphical, Kinetic, and Equilibrium Analyses of in vivo [¹²³I]β-CIT Binding to Dopamine Transporters in Healthy Human Subjects

Laruelle

Wallace

Seibyl

et al. 1994

J Cereb Blood Flow Metab

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245

128

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“…[ 123 I]-b-CIT was synthesized according to the method of Neumeyer et al (1991) with several modifications described earlier (Brücke et al, 1993). After blockade of thyroid uptake with 600 mg sodium perchlorate orally 30 min before tracer application, subjects received a mean dose of 131 MBq (717 SD; 3.5 mCi70.4 SD) [ 123 I]-b-CIT intravenously as a single bolus.…”

Section: Spect Imaging and Data Analysismentioning

confidence: 99%

[123I]-β-CIT SPECT Imaging Shows Reduced Thalamus–Hypothalamus Serotonin Transporter Availability in 24 Drug-Free Obsessive-Compulsive Checkers

Zitterl

Aigner

Stompe

et al. 2006

Neuropsychopharmacol

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Numerous findings indicate alterations in brain serotonin systems in obsessive-compulsive disorder (OCD). We investigated the in vivo availability of thalamus-hypothalamus serotonin transporters (SERT) in patients with DSM-IV OCD who displayed prominent behavioral checking compulsions (OC-checkers). Four hours after injection of [ 123 I]-2b-carbomethoxy-3b-(4-iodophenyl)tropane ([ 123 I]-b-CIT), single photon emission computed tomography (SPECT) scans were performed in 24 medication-free non-depressed OC-checkers and 24 age-and gender-matched healthy controls. For quantification of brain serotonin transporter availability, a ratio of specific to non-displaceable [ 123 I]-b-CIT brain binding was used (V 00 3 ¼ (thalamus and hypothalamusÀcerebellum)/cerebellum). Drug-free nondepressed OC-checkers showed an 18% reduced brain serotonin transporter availability in the thalamus and hypothalamus, as compared with healthy control subjects (1.3870.19 vs 1.6970.21; po0.001). There was a strong negative correlation between severity of OC symptomatology (Y-BOCS scores) and SERT availability (r ¼ À0.80; po0.001). Moreover, we found a significant positive correlation between illness duration and serotonin transporter availability (r ¼ 0.43; po0.05). This first report of significantly reduced [ 123 I]-b-CIT binding in the thalamus-hypothalamus region in OC-checkers suggests reduced brain serotonin transporter availability, which is more pronounced with increased severity of OC symptomatology and short duration of illness. The results provide direct evidence for an involvement of the serotonergic system in the pathophysiology of OCD.

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“…To date the most important tracer used with SPET for imaging the dopamine transporter is 123 I-labelled 2b-carbomethoxy-3b-(4-iodophenyl)tropane (b-CIT) (Innis et al 1991;Neumeyer et al 1991). 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).…”

Section: Dopamine Transporter In Vivo Imagingmentioning

confidence: 99%

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

Bergström¹,

Tupala²,

Tiihonen³

2001

Pharmacology & Toxicology

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Much research interest has lately been focused on the dopamine transporter function in brain. Recent findings indicate that dopamine reuptake is more like a highly regulated than a constitutive determinant of dopamine clearance. Positron emission tomography (PET) and single-photon emission tomography (SPET) offer unique methods to study dopamine transporter function. Results from in vivo PET and SPET studies correspond well with in vitro studies performed on post mortem human brain tissue. Considering some of the variances between in vitro and in vivo receptor binding phenomena it may be that the role of a compound to alter binding to monoamine uptake sites in vitro does not indicate its potential to affect monoamine transporters after administration in vivo. This discrepancy may be better understood taking into account recent studies indicating the possibility of a rapid regulation of transporter function and surface expression. Furthermore, the dopamine transporter is a fruitful target for CNS drug discovery. Fundamental nature of drug actions in vivo may be studied using demonstrated in vitro and in vivo imaging methods.

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[123I]-2.beta.-carbomethoxy-3.beta.-(4-iodophenyl)tropane: high-affinity SPECT (single photon emission computed tomography) radiotracer of monoamine reuptake sites in brain

Cited by 231 publications

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Graphical, Kinetic, and Equilibrium Analyses of in vivo [¹²³I]β-CIT Binding to Dopamine Transporters in Healthy Human Subjects

Graphical, Kinetic, and Equilibrium Analyses of in vivo [¹²³I]β-CIT Binding to Dopamine Transporters in Healthy Human Subjects

[123I]-β-CIT SPECT Imaging Shows Reduced Thalamus–Hypothalamus Serotonin Transporter Availability in 24 Drug-Free Obsessive-Compulsive Checkers

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

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[123I]-2.beta.-carbomethoxy-3.beta.-(4-iodophenyl)tropane: high-affinity SPECT (single photon emission computed tomography) radiotracer of monoamine reuptake sites in brain

Cited by 231 publications

References 0 publications

Graphical, Kinetic, and Equilibrium Analyses of in vivo [123I]β-CIT Binding to Dopamine Transporters in Healthy Human Subjects

Graphical, Kinetic, and Equilibrium Analyses of in vivo [123I]β-CIT Binding to Dopamine Transporters in Healthy Human Subjects

[123I]-β-CIT SPECT Imaging Shows Reduced Thalamus–Hypothalamus Serotonin Transporter Availability in 24 Drug-Free Obsessive-Compulsive Checkers

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

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Product

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Graphical, Kinetic, and Equilibrium Analyses of in vivo [¹²³I]β-CIT Binding to Dopamine Transporters in Healthy Human Subjects

Graphical, Kinetic, and Equilibrium Analyses of in vivo [¹²³I]β-CIT Binding to Dopamine Transporters in Healthy Human Subjects