Serotonin 1B receptor density mapping of the human brainstem using positron emission tomography and autoradiography

The serotonin 1B (5-HT1B) receptor has lately received considerable interest in relation to psychiatric and neurological diseases, partly due to findings based on quantification using Positron Emission Tomography (PET). Although the brainstem is an important structure in this regard, PET radioligand binding quantification in brainstem areas often shows poor reliability. This study aims to improve PET quantification of 5-HT1B receptor binding in the brainstem. Volumes of interest (VOIs) were selected based on a 3D [3H]AZ10419369 Autoradiography brainstem model, which visualized 5-HT1B receptor distribution in high resolution. Two previously developed VOI delineation methods were tested and compared to a conventional manual method. For a method based on template data, a [11C]AZ10419369 PET template was created by averaging parametric binding potential (BPND) images of 52 healthy subjects. VOIs were generated based on a predefined volume and BPND thresholding and subsequently applied to test-retest [11C]AZ10419369 parametric BPND images of 8 healthy subjects. For a method based on individual subject data, VOIs were generated directly on each individual parametric image. Both methods showed improved reliability compared to a conventional manual VOI. The VOIs created with [11C]AZ10419369 template data can be automatically applied to future PET studies measuring 5-HT1B receptor binding in the brainstem.

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Reproducibility of Striatal and Thalamic Dopamine D2 Receptor Binding Using [11C]raclopride with High-Resolution Positron Emission Tomography

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2010.64 ◽

2010 ◽

Vol 31 (1) ◽

pp. 155-165 ◽

Cited By ~ 28

Author(s):

Kati Alakurtti ◽

Sargo Aalto ◽

Jarkko J Johansson ◽

Kjell Någren ◽

Terhi Tuokkola ◽

...

Keyword(s):

Positron Emission Tomography ◽

High Resolution ◽

Spatial Resolution ◽

Receptor Binding ◽

Dopamine D2 Receptor ◽

Intraclass Correlation ◽

Emission Tomography ◽

Binding Potential ◽

Reference Tissue ◽

Positron Emission

Positron emission tomography (PET) imaging of small striatal brain structures such as the ventral striatum (VST) has been hampered by low spatial resolution causing partial-volume effects. The high-resolution research tomograph (HRRT) is a brain-dedicated PET scanner that has considerably better spatial resolution than its predecessors. However, its superior spatial resolution is associated with a lower signal-to-noise ratio. We evaluated the test–retest reliability of the striatal and thalamic dopamine D2 receptor binding using the HRRT scanner. Seven healthy male volunteers underwent two [11C]raclopride PET scans with a 2.5-hour interval. Dopamine D2 receptor availability was quantified as binding potential (BPND) using the simplified reference tissue model. To evaluate the reproducibility of repeated BPND estimations, absolute variability (VAR) and intraclass correlation coefficients (ICCs) were calculated. VAR values indicated fairly good reproducibility and were 3.6% to 4.5% for the caudate nucleus and putamen and 4.5% to 6.4% for the lateral and medial part of the thalamus. In the VST, the VAR value was 5.8% when the definition was made in the coronal plane. However, the ICC values were only moderate, in the range of 0.34 to 0.66, for all regions except the putamen (0.87). Experimental signal processing methods improved neither ICC nor VAR values significantly.

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Effect of Simple Motor Performance on Regional Dopamine Release in the Striatum in Parkinson Disease Patients and Healthy Subjects: A Positron Emission Tomography Study

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200206000-00013 ◽

2002 ◽

Vol 22 (6) ◽

pp. 746-752 ◽

Cited By ~ 43

Author(s):

Yasuomi Ouchi ◽

Etsuji Yoshikawa ◽

Masami Futatsubashi ◽

Hiroyuki Okada ◽

Tatsuo Torizuka ◽

...

Keyword(s):

Positron Emission Tomography ◽

Parkinson Disease ◽

Healthy Subjects ◽

Dopamine Release ◽

Dorsal Striatum ◽

Emission Tomography ◽

Binding Potential ◽

Healthy Group ◽

Logan Plot ◽

Positron Emission

To investigate changes in dopamine release in the striatum during motor exercise in human subjects with and without striatal dopamine denervation, eight healthy subjects and eight patients with Parkinson disease (PD) were measured during unilateral foot extension/flexion movement using positron emission tomography with [11C]raclopride. Five subjects in each group were later scanned in the resting condition. Estimation of binding potential (k3/k4) of [11C]raclopride was based on Logan plot method. Significant reductions in [11C]raclopride k3/k4 were found in the dorsal putamen contralateral to the exercise side in the healthy group and ipsilaterally in the PD group. Spearman rank correlation analysis showed that [11C]raclopride k3/k4 correlated inversely with the decrease in performance (velocity and motion range) in the dorsal putamen contralaterally in the healthy group and ipsilaterally in the PD group. These results suggest that simple but laborious motor exercise (motor stimulation) generates significant dopamine release in the dorsal striatum contralateral to the motor execution in humans. Lack of the crossed pattern and ipsilateral increase in dopamine release in the dorsal striatum during the unilateral limb movement may reflect the pathophysiology for hypokinetic and insufficient coordinating movement in PD.

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The impact of stereotactic pallidal surgery on the dopamine D2 receptor in Parkinson disease: a positron emission tomography study

Journal of Neurosurgery ◽

10.3171/jns.2003.98.1.0057 ◽

2003 ◽

Vol 98 (1) ◽

pp. 57-63 ◽

Cited By ~ 16

Author(s):

Takeshi Nakajima ◽

Taro Nimura ◽

Keiichiro Yamaguchi ◽

Tadashi Ando ◽

Masatoshi Itoh ◽

...

Keyword(s):

Positron Emission Tomography ◽

Parkinson Disease ◽

Receptor Binding ◽

Emission Tomography ◽

Binding Potential ◽

Yahr Stage ◽

Content Type ◽

Positron Emission ◽

The Impact ◽

Fine Print

Object. The aim of this study was to estimate the impact of stereotactic pallidal surgery on the binding potential of dopamine D2 receptors in patients with advanced Parkinson disease (PD). Methods. Six patients with advanced PD (three men and three women; mean age 56.7 ± 9.8 years, Hoehn and Yahr stage 3.3 ± 1.1/3.9 ± 1.2 [on/off scores], mean ± standard deviation) underwent stereotactic pallidal surgery. One underwent right posteroventral pallidotomy (PVP), one received left PVP, three were treated with deep brain stimulation (DBS) of the left globus pallidus internus (GPi), and one with bilateral DBS of the GPi. The binding potential of the dopamine D2 receptors of these patients was determined before and after surgery by using positron emission tomography scanning with 11C-nemonapride and it was compared with the value in eight healthy volunteers. The authors also examined whether changes in the D2 receptor binding potential were correlated with the clinical outcome. The clinical symptoms, especially those in the off state, were significantly improved after surgery. Preoperatively, the D2 receptor binding potential in the putamen was elevated by 27% (p < 0.01) and that in the thalamus was 29% lower than that in controls (p < 0.01). The D2 receptor binding potential in the putamen and thalamus returned to control levels after surgery. The preoperative level of the D2 receptor binding potential in the anterior cingulate cortex was comparable to that of controls, but it declined significantly after surgery, whereas the D2 receptor binding potential in other regions of both hemispheres showed no significant changes after surgery. Although the D2 receptor binding potential did not correlate with the Hoehn and Yahr stage, the Schwab and England score, or the Unified PD Rating Scale (UPDRS) score, a positive correlation was seen between the percent improvement rate of the total UPDRS score in the off state and the percentage change of the D2 receptor binding potential in the putamen (r = 0.773, p = 0.0417 according to the Pearson linear correlation). Conclusions. The altered dopamine D2 receptor binding potential in the putamen might play a crucial role in clinical improvement after PVP or DBS of the GPi in advanced PD.

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