Dopamine D-2 receptor imaging radiopharmaceuticals: synthesis, radiolabeling and in vitro binding of (R)-(+)- and (S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide

Kung, Hank F.; Kasliwal, Ravindra; Pan, Sangren; Kung, Mei Ping; Mach, Robert H.; Guo, Yu

doi:10.1021/jm00400a027

Cited by 79 publications

(29 citation statements)

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“…SPECT procedure [99 m Tc]TRODAT-1 was prepared as described elsewhere [20,21,26,27], and [123 I]IBZM [19] was purchased commercially. The kinetics of TRODAT-1 binding had been analysed in earlier experiments [13,21].…”

Section: Assessment Of Psychopathologymentioning

confidence: 99%

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Dual-isotope SPECT imaging of striatal dopamine: a comparative study between never-treated and haloperidol-treated first-episode schizophrenic patients

Schmitt

Dresel

Frodl

et al. 2011

Eur Arch Psychiatry Clin Neurosci

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The aim of this dual-isotope SPECT imaging study was to evaluate striatal dopamine transporter (DAT) and D2 receptor availability in first-episode never-treated and haloperidol-treated schizophrenic patients and whether the availability is associated with psychopathology. Twenty-four inpatients with a first acute schizophrenic episode were enrolled in the study; 12 of these patients were treated with haloperidol for 2 weeks before dual-isotope SPECT was performed, whereas the other 12 patients underwent the SPECT evaluation directly after enrollment. Twelve healthy control persons were also recruited and evaluated with the dual-isotope SPECT protocol. Psychopathology was assessed by the Positive and Negative Syndrome Scale and other scales. D2-radioligand binding did not differ between drug-naïve patients and the control group but was significantly lower in the haloperidol-treated group. DAT availability was also significantly lower in the haloperidol patients than in the other two groups and differed significantly between drug-naïve, positive-syndrome-type patients and healthy controls. The data obtained with the new dual-isotope SPECT technique reveal a direct effect of haloperidol at the D2 and DAT receptor level.

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Section: Assessment Of Psychopathologymentioning

confidence: 99%

“…Haloperidol treatment was given for a mean of 14.83 days (14.83 ± 2.86, range [11][12][13][14][15][16][17][18][19][20]. The mean daily dose was 12.63 mg (12.63 ± 5.30, range [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], and the mean dose per kg body weight (BW) was 0.17 mg/kg (0.17 ± 0.075, range 0.04-0.27).…”

Section: Haloperidol Treatmentmentioning

confidence: 99%

Dual-isotope SPECT imaging of striatal dopamine: a comparative study between never-treated and haloperidol-treated first-episode schizophrenic patients

Schmitt

Dresel

Frodl

et al. 2011

Eur Arch Psychiatry Clin Neurosci

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“…Statistical comparisons were done with data expressed in fentomole per microliter of dialysate, corrected for in vitro recovery. (Kung et al, 1988b; (Kessler et al, 1991). Labeling of [ 123 I]IBF and [ 123 I]IBZM was performed as previously described (Al-Tikriti et al, 1994;Kung et al, 1988a;Kung, 1990, Murphy et al, 1990).…”

Section: Microdialysis Experimentsmentioning

confidence: 99%

Microdialysis and SPECT measurements of amphetamine-induced dopamine release in nonhuman primates

Laruelle

Iyer

Al-Tikriti

et al. 1997

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259

150

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The competition between endogenous transmitters and radiolabeled ligands for in vivo binding to neuroreceptors might provide a method to measure endogenous transmitter release in the living human brain with noninvasive techniques such as positron emission tomography (PET) or single photon emission computerized tomography (SPECT). In this study, we validated the measure of amphetamine-induced dopamine release with SPECT in nonhuman primates. Microdialysis experiments were conducted to establish the dose-response curve of amphetamine-induced dopamine release and to document how pretreatment with the dopamine depleter alpha-methyl-para-tyrosine (alpha MPT) affects this response. SPECT experiments were performed with two iodinated benzamides, [123I]IBZM and [123I]IBF, under sustained equilibrium condition. Both radio-tracers are specific D2 antagonists, but the affinity of [123I]IBZM (KD-0.4 nM) is lower than that of [123I]IBF (KD 0.1 nM). With both tracers, we observed a prolonged reduction in binding to D2 receptors following amphetamine injection. [123I]IBZM binding to D2 receptors was more affected than [123I]IBF by high doses of amphetamine, indicating that a lower affinity increases the vulnerability of a tracer to endogenous competition. With [123I]IBZM, we observed an excellent correlation between reduction of D2 receptor binding measured with SPECT and peak dopamine release measured with microdialysis after various doses of amphetamine. Pretreatment with alpha MPT significantly reduced the effect of amphetamine on [123I]IBZM binding to D2 receptors, confirming that this effect was mediated by intrasynaptic dopamine release. Together, these results validate the use of this SPECT paradigm as a noninvasive measurement of intrasynaptic dopamine release in the living brain.

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“…The first generation of PET and SPECT D 2 receptor radiotracers, such as [ 11 C]raclopride Farde et al 1985) and [ 123 I]IBZM (Kung et al 1988), enabled the imaging of D 2 receptors only in the striatum, the brain area with the highest D 2 density. More recently, new "high affinity" PET and SPECT D 2 receptor radiotracers such as [ 11 C]FLB 457 (Halldin et al 1995), [ 18 F]fallypride (Mukherjee et al 1995b) and [ 123 I]epidepride (Kessler et al 1992) have been introduced.…”

Section: Introductionmentioning

confidence: 99%

In vivo affinity of [18F]fallypride for striatal and extrastriatal dopamine D2 receptors in nonhuman primates

et al. 2004

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The in vivo affinity of [18F]fallypride was not as high as previously estimated from in vitro values. This property might contribute to the favorable kinetic properties of the tracer. The in vivo affinity was similar between striatal and extrastriatal regions. This result indicates that the measured regional in vivo affinities of this tracer are not affected by putative regional differences in endogenous dopamine, and that [18F]fallypride is an appropriate tool to provide unbiased estimates of the occupancy of D2 receptors by antipsychotic drugs in striatal and extrastriatal regions.

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Dopamine D-2 receptor imaging radiopharmaceuticals: synthesis, radiolabeling and in vitro binding of (R)-(+)- and (S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide

Cited by 79 publications

References 0 publications

Dual-isotope SPECT imaging of striatal dopamine: a comparative study between never-treated and haloperidol-treated first-episode schizophrenic patients

Dual-isotope SPECT imaging of striatal dopamine: a comparative study between never-treated and haloperidol-treated first-episode schizophrenic patients

Microdialysis and SPECT measurements of amphetamine-induced dopamine release in nonhuman primates

In vivo affinity of [18F]fallypride for striatal and extrastriatal dopamine D2 receptors in nonhuman primates

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