SPECT imaging of D2 dopamine receptors and endogenous dopamine release in mice

Jongen, Cynthia; Bruin, Kora de; Beekman, Freek J.; Booij, Jan

doi:10.1007/s00259-008-0795-0

Cited by 16 publications

(11 citation statements)

References 22 publications

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“…In this study, challenge with 2.5 mg/kg amphetamine or 5 mg/kg methylphenidate induced a 21 % reduction of D 2 receptor binding relative to baseline (Schiffer et al , 2006 ). Moreover, comparable results were obtained in a later in vivo imaging study on mice which was performed with the highly-resolving U-SPECT (Jongen et al , 2008 ); in this investigation, application of 2.5 mg/kg amphetamine was found to induce a 27 % reduction of [ 123 I]IBZM binding compared with baseline.…”

Section: Discussionsupporting

confidence: 78%

Pharmacological challenge and synaptic response – assessing dopaminergic function in the rat striatum with small animal single-photon emission computed tomography (SPECT) and positron emission tomography (PET)

Nikolaus

Larisch

Vosberg

et al. 2011

Reviews in the Neurosciences

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Disturbances of dopaminergic neurotransmission may be caused by changes in concentrations of synaptic dopamine (DA) and/or availabilities of pre- and post-synaptic transporter and receptor binding sites. We present a series of experiments which focus on the regulatory mechanisms of the dopamin(DA)ergic synapse in the rat striatum. In these studies, DA transporter (DAT) and/or D(2) receptor binding were assessed with either small animal single-photon emission computed tomography (SPECT) or positron emission tomography (PET) after pharmacological challenge with haloperidol, L-DOPA and methylphenidate, and after nigrostriatal 6-hydroxydopamine lesion. Investigations of DAT binding were performed with [(123)I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ([(123)I]FP-CIT). D(2) receptor bindingd was assessed with either [(123)I](S)-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide ([(123)I]IBZM) or [(18)F]1[3-(4'fluorobenzoyl)propyl]-4-(2-keto-3-methyl-1-benzimidazolinyl)piperidine ([(18)F]FMB). Findings demonstrate that in vivo investigations of transporter and/or receptor binding are feasible with small animal SPECT and PET. Therefore, tracers that are radiolabeled with isotopes of comparatively long half-lives such as (123)I may be employed. Our approach to quantify DAT and/or D(2) receptor binding at baseline and after pharmacological interventions inducing DAT blockade, D(2) receptor blockade, and increases or decreases of endogenous DA concentrations holds promise for the in vivo assessment of synaptic function. This pertains to animal models of diseases associated with pre- or postsynaptic DAergic deficiencies such as Parkinson's disease, Huntington's disease, attention-deficit/hyperactivity disorder, schizophrenia or drug abuse.

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Section: Discussionsupporting

confidence: 78%

Pharmacological challenge and synaptic response – assessing dopaminergic function in the rat striatum with small animal single-photon emission computed tomography (SPECT) and positron emission tomography (PET)

Nikolaus

Larisch

Vosberg

et al. 2011

Reviews in the Neurosciences

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“…This paradigm is widely employed to assess the function of presynaptic dopaminergic terminals (Ginovart, 2005;Laruelle, 2000). Dopamine is thought to act on [ 123 I]IBZM binding by direct competitive antagonistic binding to the D 2/3 receptor (thereby augmenting the appK d ) as well as by provoking receptors' endocytosis, thereby diminishing receptor concentration that is available for binding (Ginovart et al, 2004;Jongen et al, 2008;Skinbjerg et al, 2010;Sun et al, 2003). Given the complexity of this phenomenon and the potential biological implications, the partial saturation protocol could provide a simple method to assess the impact of the amphetamine challenge on both B avail and appK d .…”

Section: Non-invasive Estimation Of B Avail and Appk D Using A Partiamentioning

confidence: 99%

A single-scan protocol for absolute D2/3 receptor quantification with [123I]IBZM SPECT

et al. 2017

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A partial saturation protocol permits the non-invasive and time-efficient estimation of B and appK separately. Given the different biological phenomena that underlie these parameters, this method may be applied for the in-depth study of the dopaminergic system in translational molecular imaging studies. It can detect the biological variations in these parameters, dissociating the variations in receptor density (B) from affinity (1/appK), which reflects the interactions of the receptor with its endogenous ligand.

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“…The purpose of this study is to indicate the theoretical levels of spatial resolution that we might achieve with our current multi-pinhole system and the projection magnification on the front and back detectors. Using the same camera figuration we simulated projection data from a more realistic phantom of a mouse brain (figure 15) with an activity ratio of 7:1 between striatum and the rest of the brain, which was roughly estimated based on an in vivo mouse brain study (Jongen et al 2008). The projection images of this phantom on one of the front detectors and one of the back detectors is presented in figure 16.…”

Section: Methodsmentioning

confidence: 99%

Multi-pinhole collimator design for small-object imaging with SiliSPECT: a high-resolution SPECT

et al. 2008

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We have designed a multi-pinhole collimator for a dual-headed, stationary SPECT system that incorporates high-resolution silicon double-sided strip detectors. The compact camera design of our system enables imaging at source-collimator distances between 20 and 30 mm. Our analytical calculations show that using knife-edge pinholes with small-opening angles or cylindrically shaped pinholes in a focused, multi-pinhole configuration in combination with this camera geometry can generate narrow sensitivity profiles across the field of view that can be useful for imaging small objects at high sensitivity and resolution. The current prototype system uses two collimators each containing 127 cylindrically shaped pinholes that are focused toward a target volume. Our goal is imaging objects such as a mouse brain, which could find potential applications in molecular imaging.

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SPECT imaging of D2 dopamine receptors and endogenous dopamine release in mice

Cited by 16 publications

References 22 publications

Pharmacological challenge and synaptic response – assessing dopaminergic function in the rat striatum with small animal single-photon emission computed tomography (SPECT) and positron emission tomography (PET)

Pharmacological challenge and synaptic response – assessing dopaminergic function in the rat striatum with small animal single-photon emission computed tomography (SPECT) and positron emission tomography (PET)

A single-scan protocol for absolute D2/3 receptor quantification with [123I]IBZM SPECT

Multi-pinhole collimator design for small-object imaging with SiliSPECT: a high-resolution SPECT

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