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Jogeshwar Mukherjee - One of the best experts on this subject based on the ideXlab platform.

  • Dopamine receptor density and white mater integrity: ^18F-Fallypride positron emission tomography and diffusion tensor imaging study in healthy and schizophrenia subjects
    Brain Imaging and Behavior, 2020
    Co-Authors: Semen A. Mitelman, Bradley T Christian, Bradley R Buchsbaum, Jogeshwar Mukherjee, Monte S. Buchsbaum, Brian M. Merrill, Douglas S Lehrer
    Abstract:

    Dopaminergic dysfunction and changes in white matter integrity are among the most replicated findings in schizophrenia. A modulating role of dopamine in myelin formation has been proposed in animal models and healthy human brain, but has not yet been systematically explored in schizophrenia. We used diffusion tensor imaging and ^18F-Fallypride positron emission tomography in 19 healthy and 25 schizophrenia subjects to assess the relationship between gray matter dopamine D_2/D_3 receptor density and white matter fractional anisotropy in each diagnostic group. AFNI regions of interest were acquired for 42 cortical Brodmann areas and subcortical gray matter structures as well as stereotaxically placed in representative white matter areas implicated in schizophrenia neuroimaging literature. Welch’s t-test with permutation-based p value adjustment was used to compare means of z-transformed correlations between fractional anisotropy and ^18F-Fallypride binding potentials in hypothesis-driven regions of interest in the diagnostic groups. Healthy subjects displayed an extensive pattern of predominantly negative correlations between ^18F-Fallypride binding across a range of cortical and subcortical gray matter regions and fractional anisotropy in rostral white matter regions (internal capsule, frontal lobe, anterior corpus callosum). These patterns were disrupted in subjects with schizophrenia, who displayed significantly weaker overall correlations as well as comparatively scant numbers of significant correlations with the internal capsule and frontal (but not temporal) white matter, especially for dopamine receptor density in thalamic nuclei. Dopamine D_2/D_3 receptor density and white matter integrity appear to be interrelated, and their decreases in schizophrenia may stem from hyperdopaminergia with dysregulation of dopaminergic impact on axonal myelination.

  • positive association between cerebral grey matter metabolism and dopamine d2 d3 receptor availability in healthy and schizophrenia subjects an 18f fluorodeoxyglucose and 18f Fallypride positron emission tomography study
    World Journal of Biological Psychiatry, 2020
    Co-Authors: Semen A. Mitelman, Bradley T Christian, Bradley R Buchsbaum, Jogeshwar Mukherjee, Monte S. Buchsbaum, Brian Merrill, Douglas S Lehrer
    Abstract:

    : Objectives: Overlapping decreases in extrastriatal dopamine D2/D3-receptor availability and glucose metabolism have been reported in subjects with schizophrenia. It remains unknown whether these findings are physiologically related or coincidental. Methods: To ascertain this, we used two consecutive 18F-fluorodeoxyglucose and 18F-Fallypride positron emission tomography scans in 19 healthy and 25 unmedicated schizophrenia subjects. Matrices of correlations between 18F-fluorodeoxyglucose uptake and 18F-Fallypride binding in voxels at the same xyz location and AFNI-generated regions of interest were evaluated in both diagnostic groups. Results:18F-fluorodeoxyglucose uptake and 18F-Fallypride binding potential were predominantly positively correlated across the striatal and extrastriatal grey matter in both healthy and schizophrenia subjects. In comparison to healthy subjects, significantly weaker correlations in subjects with schizophrenia were confirmed in the right cingulate gyrus and thalamus, including the mediodorsal, lateral dorsal, anterior, and midline nuclei. Schizophrenia subjects showed decreased D2/D3-receptor availability in the hypothalamus, mamillary bodies, thalamus and several thalamic nuclei, and increased glucose uptake in three lobules of the cerebellar vermis. Conclusions: Dopaminergic system may be involved in modulation of grey matter metabolism and neurometabolic coupling in both healthy human brain and psychopathology. Hyperdopaminergic state in untreated schizophrenia may at least partly account for the corresponding decreases in grey matter metabolism.

  • d2 d3 dopamine receptor binding with f 18 Fallypride correlates of executive function in medication naive patients with schizophrenia
    Schizophrenia Research, 2018
    Co-Authors: Bradley T Christian, Douglas S Lehrer, Monte S. Buchsbaum, Brian Merrill, Nora S. Vyas, Alex Decastro, Nicholas A. Doninger, Jogeshwar Mukherjee
    Abstract:

    Converging evidence indicates that the prefrontal cortex is critically involved in executive control and that executive dysfunction is implicated in schizophrenia. Reduced dopamine D2/D3 receptor binding potential has been reported in schizophrenia, and the correlations with neuropsychological test scores have been positive and negative for different tasks. The aim of this study was to examine the relation between dopamine D2/D3 receptor levels with frontal and temporal neurocognitive performance in schizophrenia. Resting-state 18F-Fallypride positron emission tomography was performed on 20 medication-naive and 5 previously medicated for brief earlier periods patients with schizophrenia and 19 age- and sex-matched healthy volunteers. Striatal and extra-striatal dopamine D2/D3 receptor levels were quantified as binding potential using Fallypride imaging. Magnetic resonance images in standard Talairach position and segmented into gray and white matter were co-registered to the Fallypride images, and the AFNI stereotaxic atlas was applied. Two neuropsychological tasks known to activate frontal and temporal lobe function were chosen, specifically the Wisconsin Card Sorting Test (WCST) and the California Verbal Learning Test (CVLT). Images of the correlation coefficient between Fallypride binding and WCST and CVLT performance showed a negative correlation in contrast to positive correlations in healthy volunteers. The results of this study demonstrate that lower Fallypride binding potential in patients with schizophrenia may be associated with better performance. Our findings are consistent with previous studies that failed to find cognitive improvements with typical dopamine-blocking medications.

  • D2/D3 dopamine receptor binding with [F-18]Fallypride correlates of executive function in medication-naïve patients with schizophrenia.
    Schizophrenia research, 2017
    Co-Authors: Nora S. Vyas, Bradley T Christian, Douglas S Lehrer, Monte S. Buchsbaum, Brian Merrill, Alex Decastro, Nicholas A. Doninger, Jogeshwar Mukherjee
    Abstract:

    Converging evidence indicates that the prefrontal cortex is critically involved in executive control and that executive dysfunction is implicated in schizophrenia. Reduced dopamine D2/D3 receptor binding potential has been reported in schizophrenia, and the correlations with neuropsychological test scores have been positive and negative for different tasks. The aim of this study was to examine the relation between dopamine D2/D3 receptor levels with frontal and temporal neurocognitive performance in schizophrenia. Resting-state 18F-Fallypride positron emission tomography was performed on 20 medication-naive and 5 previously medicated for brief earlier periods patients with schizophrenia and 19 age- and sex-matched healthy volunteers. Striatal and extra-striatal dopamine D2/D3 receptor levels were quantified as binding potential using Fallypride imaging. Magnetic resonance images in standard Talairach position and segmented into gray and white matter were co-registered to the Fallypride images, and the AFNI stereotaxic atlas was applied. Two neuropsychological tasks known to activate frontal and temporal lobe function were chosen, specifically the Wisconsin Card Sorting Test (WCST) and the California Verbal Learning Test (CVLT). Images of the correlation coefficient between Fallypride binding and WCST and CVLT performance showed a negative correlation in contrast to positive correlations in healthy volunteers. The results of this study demonstrate that lower Fallypride binding potential in patients with schizophrenia may be associated with better performance. Our findings are consistent with previous studies that failed to find cognitive improvements with typical dopamine-blocking medications.

  • 79. D2/D3 Dopamine Receptor Binding With [F-18] Fallypride Correlates of Executive Function in Medication-Naive Patients With Schizophrenia.
    Schizophrenia Bulletin, 2017
    Co-Authors: Monte S. Buchsbaum, Bradley T Christian, Douglas S Lehrer, Nora S. Vyas, Brian Merill, Alex Decastro, Nicholas Donninger, Jogeshwar Mukherjee
    Abstract:

    Abstract Background: Converging evidence indicates that the prefrontal cortex is critically involved in executive control and that executive dysfunction is implicated in schizophrenia. Reduced dopamine D2/D3 receptor binding potential has been reported in schizophrenia, and the correlations with neuropsychological test scores have been positive and negative for different tasks. The aim of this study was to examine the relation between dopamine D2/D3 receptor levels with frontal and temporal neurocognitive performance in schizophrenia. Methods: Resting-state 18F-Fallypride positron emission tomography was performed on 20 medication-naive and 5 previously medicated for brief earlier periods patients with schizophrenia and 19 age- and sex-matched normal controls. Striatal and extra-striatal dopamine D2/D3 receptor levels were quantified as binding potential using Fallypride imaging. Magnetic resonance images in standard Talairach position and segmented into gray and white matter were co-registered to the Fallypride images, and the AFNI stereotaxic atlas was applied. Two neuropsychological tasks known to activate frontal and temporal lobe function were chosen, specifically the Wisconsin Card Sorting Test (WCST) and the California Verbal Learning Test (CVLT). Results: Images of the correlation coefficient between Fallypride binding and WCST and CVLT performance showed a negative correlation in contrast to positive correlations in healthy volunteers. Prefrontal Brodmann area 10 and striatal areas showed the greatest differences. Heat maps of correlation patterns of Fallypride binding potential and neuropsychological performance were obtained. Differences in correlation patterns between healthy volunteers and patients were confirmed with Monte Carlo permutation analysis. Correlation coefficient histograms also showed significant differences in shape. Conclusion: The results of this study demonstrate that lower Fallypride binding potential in patients with schizophrenia may be associated with better performance and consistent with previous studies that failed to find cognitive improvement with typical dopamine-blocking medications.

Min-liang Pan - One of the best experts on this subject based on the ideXlab platform.

  • 18F-Fallypride PET of Pancreatic Islets: In Vitro and In Vivo Rodent Studies
    2016
    Co-Authors: Adriana Garcia, Norah Milne, Mohammad Mirbolooki, Min-liang Pan, Cristian Constantinescu, Ping H. Wang, Evegueni Sevrioukov, Jonathan Lakey, Jogeshwar Mukherjee
    Abstract:

    Islet cell loss in the pancreas results in diabetes. A noninvasive method that measures islet cell loss and also tracks the fate of transplanted islets would facilitate the development of novel therapeutics and improve the management of diabetes. We describe a novel dopamine D2/D3 receptor (D2/D3R)–based PET method to study islet cells in the rat pancreas and in islet cell transplantation. Methods: 18F-Fallypride binding to isolated rat islets and pancreas was evaluated in the absence and presence of the D2/D3R inhibitor haloperidol. After intravenous 18F-fall-ypride (28–37 MBq) administration, normal rats and rats pre-treated with haloperidol were imaged in a PET/CT scanner and subsequently studied ex vivo for 18F-Fallypride localization in the pancreas. A streptozotocin-treated diabetic rat model was used to study localization of 18F-Fallypride in the pancreas, in vitro and ex vivo. Rat islet cells were transplanted into th

  • Dopamine D3 receptor binding of (18)F-Fallypride: Evaluation using in vitro and in vivo PET imaging studies.
    Synapse (New York N.Y.), 2015
    Co-Authors: Jogeshwar Mukherjee, Cristian Constantinescu, Angela T. Hoang, Taleen Jerjian, Divya Majji, Min-liang Pan
    Abstract:

    Identification of dopamine D3 receptors (D3R) in vivo is important to understand several brain functions related to addiction. The goal of this work was to identify D3R binding of the dopamine D2 receptor (D2R)/D3R imaging agent, (18)F-Fallypride. Brain slices from male Sprague-Dawley rats (n = 6) and New Zealand White rabbits (n = 6) were incubated with (18)F-Fallypride and D3R selective agonist (R)-7-OH-DPAT (98-fold D3R selective). Rat slices were also treated with BP 897 (68-fold D3R selective partial agonist) and NGB 2904 (56-fold D3R selective antagonist). In vivo rat studies (n = 6) were done on Inveon PET using 18-37 MBq (18)F-Fallypride and drug-induced displacement by (R)-7-OH-DPAT, BP 897 and NGB 2904. PET/CT imaging of wild type (WT, n = 2) and D2R knock-out (KO, n = 2) mice were carried out with (18)F-Fallypride. (R)-7-OH-DPAT displaced binding of (18)F-Fallypride, both in vitro and in vivo. In vitro, at 10 nM (R)-7-OH-DPAT, (18)F-Fallypride binding in the rat ventral striatum (VST) and dorsal striatum (DST) and rabbit nucleus accumbens were reduced by ∼10-15%. At 10 μM (R)-7-OH-DPAT all regions in rat and rabbit were reduced by ≥85%. In vivo reductions for DST and VST before and after (R)-7-OH-DPAT were: low-dose (0.015 mg kg(-1)) DST -22%, VST -29%; high-dose (1.88 mg kg(-1)) DST -58%, VST -77%, suggesting D3R/D2R displacement. BP 897 and NGB 2904 competed with (18)F-Fallypride in vitro, but unlike BP 897, NGB 2904 did not displace (18)F-Fallypride in vivo. The D2R KO mice lacked (18)F-Fallypride binding in the DST. In summary, our findings suggest that up to 20% of (18)F-Fallypride may be bound to D3R sites in vivo.

  • spinal cord dopamine d2 d3 receptors in vivo and ex vivo imaging in the rat using 18f 11c Fallypride
    Nuclear Medicine and Biology, 2014
    Co-Authors: Jasmeet Kaur, Min-liang Pan, Cristian Constantinescu, Armen Khararjian, Robert Coleman, Jogeshwar Mukherjee
    Abstract:

    Abstract Objectives The spinal cord is known to be innervated with dopaminergic cells with catecholaminergic projections arising from the medulla and pons and dopaminergic transmission in the spinal cord is vital for sensory and motor function. Our goal was to evaluate and compare the imaging capability of dopamine D2/D3 receptors in the rat spinal cord using PET ligands 18 F-Fallypride and 11 C-Fallypride. Methods Male Sprague–Dawley rats were used in all in vitro and in vivo studies. Spinal cord and brain sections were used for in vitro autoradiography and ex vivo autoradiography. For in vivo studies animals received a 18 F-Fallypride scan or a 11 C-Fallypride PET scan. The spinal cord and the brain were then harvested, flash-frozen and imaged ex vivo. For in vivo analysis Logan plots with cerebellum as a reference was used to evaluate binding potentials (BP). Tissue ratios were used for ex vivo analysis. Drug effects were evaluated using clozapine, haloperidol and dopamine were evaluated on spinal cord sections in vitro. Results In vitro studies showed 18 F-Fallypride binding to superficial dorsal horn (SDH), dorsal horn (DH), ventral horn (VH) and the pars centralis (PC). In the cervical section, the greatest amount of binding appeared to be in the SDH. Ex vivo studies showed approximately 6% of 18 F-Fallypride in SDH compared to that observed in the striatum. In vivo analysis of both 18 F-Fallypride and 11 C-Fallypride in the spinal cord were comparable to that in the extrastriatal regions. Haloperidol and clozapine displaced more than 75% of the 18 F-Fallypride in spinal cord sections. Conclusions Our studies showed 18 F-Fallypride and 11 C-Fallypride binding in the spinal cord in vitro and in vivo. The binding pattern correlates well with the known distribution of dopamine D2/D3 receptors in the spinal cord.

  • imaging pancreas in healthy and diabetic rodent model using 18f Fallypride positron emission tomography computed tomography
    Diabetes Technology & Therapeutics, 2014
    Co-Authors: Adriana Garcia, Min-liang Pan, Archana Venugopal, Jogeshwar Mukherjee
    Abstract:

    Abstract Background: A noninvasive method of monitoring the loss of islet cells can provide an earlier and improved diagnosis for therapeutics development of preclinical phases of diabetes. The use of [18F]Fallypride, a dopamine D2/D3 receptor radiotracer, has been developed as a surrogate marker to evaluate loss of pancreatic islet cells in a rodent model of type 1 diabetes. Materials and Methods: Healthy Sprague–Dawley rats were administered [18F]Fallypride and imaged for 2 h in a positron emission tomography (PET)/computed tomography (CT) scan. Diabetes was then induced in the same rats by administration of streptozotocin, and a PET/CT scan was performed 4 days after establishing diabetes. Pancreata of a separate set of rats were evaluated by insulin immunostaining for loss of islet cells by streptozotocin. Results: Blood glucose levels of 125 mg/dL and 550 mg/dL were established for those rats without and with diabetes, respectively. [18F]Fallypride uptake in the pancreas of both groups of rats was ra...

  • Spinal cord dopamine D2/D3 receptors: in vivo and ex vivo imaging in the rat using 18F/11C-Fallypride
    Nuclear medicine and biology, 2014
    Co-Authors: Jasmeet Kaur, Min-liang Pan, Cristian Constantinescu, Armen Khararjian, Robert Coleman, Jogeshwar Mukherjee
    Abstract:

    Abstract Objectives The spinal cord is known to be innervated with dopaminergic cells with catecholaminergic projections arising from the medulla and pons and dopaminergic transmission in the spinal cord is vital for sensory and motor function. Our goal was to evaluate and compare the imaging capability of dopamine D2/D3 receptors in the rat spinal cord using PET ligands 18 F-Fallypride and 11 C-Fallypride. Methods Male Sprague–Dawley rats were used in all in vitro and in vivo studies. Spinal cord and brain sections were used for in vitro autoradiography and ex vivo autoradiography. For in vivo studies animals received a 18 F-Fallypride scan or a 11 C-Fallypride PET scan. The spinal cord and the brain were then harvested, flash-frozen and imaged ex vivo. For in vivo analysis Logan plots with cerebellum as a reference was used to evaluate binding potentials (BP). Tissue ratios were used for ex vivo analysis. Drug effects were evaluated using clozapine, haloperidol and dopamine were evaluated on spinal cord sections in vitro. Results In vitro studies showed 18 F-Fallypride binding to superficial dorsal horn (SDH), dorsal horn (DH), ventral horn (VH) and the pars centralis (PC). In the cervical section, the greatest amount of binding appeared to be in the SDH. Ex vivo studies showed approximately 6% of 18 F-Fallypride in SDH compared to that observed in the striatum. In vivo analysis of both 18 F-Fallypride and 11 C-Fallypride in the spinal cord were comparable to that in the extrastriatal regions. Haloperidol and clozapine displaced more than 75% of the 18 F-Fallypride in spinal cord sections. Conclusions Our studies showed 18 F-Fallypride and 11 C-Fallypride binding in the spinal cord in vitro and in vivo. The binding pattern correlates well with the known distribution of dopamine D2/D3 receptors in the spinal cord.

Paul Cumming - One of the best experts on this subject based on the ideXlab platform.

  • relationship of self transcendence traits with in vivo dopamine d2 3 receptor availability and functional connectivity an 18 f Fallypride pet and fmri study
    Synapse, 2019
    Co-Authors: Paul Cumming, Jeong-hee Kim, Yi Seul Choe, Young-don Son, Hang-keun Kim, Yo Han Joo, Jong-hoon Kim
    Abstract:

    Genetic research has implicated dopamine neurotransmission in the expression of the self-transcendence trait in humans. However, molecular imaging of dopaminergic markers is undocumented in relation to this personality trait. In this multimodal imaging study, we first investigated the relationship between the self-transcendence trait and in vivo dopamine D2/3 receptor availability using [18 F]Fallypride positron emission tomography (PET). We next conducted seed-based functional connectivity analyses using resting-state functional magnetic resonance imaging (rs-fMRI) data with regions derived from the PET analysis as seeds to explore the functional significance of D2/3 receptor availability foci associated with the self-transcendence trait. Twenty-one healthy subjects underwent high-resolution PET with [18 F]Fallypride and a subset of 18 subjects also completed 3-Tesla rs-fMRI. The Temperament and Character Inventory was used to measure the self-transcendence trait. A voxel-based whole brain analysis revealed that the [18 F]Fallypride binding potential (BPND ) within the cluster of the left insula was significantly positively correlated with self-transcendence trait scores. A region-of-interest analysis also showed a significant positive correlation between self-transcendence and [18 F]Fallypride BPND in the left insula. The exploratory [18 F]Fallypride BPND seed-based rs-fMRI analysis showed that the functional connectivity from the left insula seed to the prefrontal cortices (including the inferior frontal region) was negatively associated with self-transcendence trait scores. The results of the present study suggest that D2/3 receptor-mediated neurotransmission in the left insula may constitute a significant neurobiological factor in the self-transcendence trait. The negative associations between BPND seed-based functional connectivity and self-transcendence trait scores may suggest reduced prefrontal control in this personality trait.

  • Relationship of self-transcendence traits with in vivo dopamine D2/3 receptor availability and functional connectivity: An [18 F]Fallypride PET and fMRI study.
    Synapse (New York N.Y.), 2019
    Co-Authors: Jeong-hee Kim, Paul Cumming, Yi Seul Choe, Young-don Son, Hang-keun Kim, Yo Han Joo, Jong-hoon Kim
    Abstract:

    Genetic research has implicated dopamine neurotransmission in the expression of the self-transcendence trait in humans. However, molecular imaging of dopaminergic markers is undocumented in relation to this personality trait. In this multimodal imaging study, we first investigated the relationship between the self-transcendence trait and in vivo dopamine D2/3 receptor availability using [18 F]Fallypride positron emission tomography (PET). We next conducted seed-based functional connectivity analyses using resting-state functional magnetic resonance imaging (rs-fMRI) data with regions derived from the PET analysis as seeds to explore the functional significance of D2/3 receptor availability foci associated with the self-transcendence trait. Twenty-one healthy subjects underwent high-resolution PET with [18 F]Fallypride and a subset of 18 subjects also completed 3-Tesla rs-fMRI. The Temperament and Character Inventory was used to measure the self-transcendence trait. A voxel-based whole brain analysis revealed that the [18 F]Fallypride binding potential (BPND ) within the cluster of the left insula was significantly positively correlated with self-transcendence trait scores. A region-of-interest analysis also showed a significant positive correlation between self-transcendence and [18 F]Fallypride BPND in the left insula. The exploratory [18 F]Fallypride BPND seed-based rs-fMRI analysis showed that the functional connectivity from the left insula seed to the prefrontal cortices (including the inferior frontal region) was negatively associated with self-transcendence trait scores. The results of the present study suggest that D2/3 receptor-mediated neurotransmission in the left insula may constitute a significant neurobiological factor in the self-transcendence trait. The negative associations between BPND seed-based functional connectivity and self-transcendence trait scores may suggest reduced prefrontal control in this personality trait.

  • The role of striatal dopamine D_2/3 receptors in cognitive performance in drug-free patients with schizophrenia
    Psychopharmacology, 2018
    Co-Authors: Tanja Veselinović, Paul Cumming, Ingo Vernaleken, Hildegard Janouschek, Michael Paulzen, Felix M. Mottaghy, Gerhard Gründer
    Abstract:

    Objective A considerable body of research links cognitive function to dopaminergic transmission in the prefrontal cortex, but less is known about cognition in relation to striatal dopamine D_2/3 receptors in unmedicated patients with psychosis. Methods We investigated this association by obtaining PET recordings with the high-affinity D_2/3 antagonist ligand [^18F] Fallypride in 15 medication-free patients with schizophrenia and 11 healthy controls. On the day of PET scanning, we undertook comprehensive neuropsychological testing and assessment of psychopathology using the Positive and Negative Syndrome Scale (PANSS). Results The patients’ performance in cognitive tests was significantly impaired in almost all domains. Irrespective of medication history, the mean [^18F] Fallypride binding potential ( BP _ ND ) in the patient group tended to be globally 5–10% higher than that of the control group, but without reaching significance in any brain region. There were significant positive correlations between individual patient performance in the Trail Making Test (TMT(A) and TMT(B)) and Digit-Symbol-Substitution-Test with regional [^18F] Fallypride BP _ ND , which remained significant after Bonferroni correction for the TMT(A) in caudate nucleus (CN) and for the TMT(B) in CN and putamen. No such correlations were evident in the control group. Discussion The association between better cognitive performance and greater BP _ ND in schizophrenia patients may imply that relatively lower receptor occupancy by endogenous dopamine favors better sparing of cognitive function. Absence of comparable correlations in healthy controls could indicate a greater involvement of signaling at dopamine D_2/3 receptors in certain cognitive functions in schizophrenia patients than in healthy controls.

  • Validation of the Octamouse for Simultaneous 18F-Fallypride Small-Animal PET Recordings from 8 Mice
    2016
    Co-Authors: Axel Rominger, Erik Mille, Franz Josef Gildehaus, Peter Bartenstein, Shanshan Zhang, Sebastian Nowak, Paul Cumming
    Abstract:

    Data collection in preclinical small-animal PET studies has been hindered by the small number of recordings typically obtained for a single radiosynthesis. Therefore, we tested procedures for obtaining 8 simultaneous small-animal PET recordings from the brains of 8 mice. Methods: The effect of scatter correction on the small-animal PET recordings was first evaluated in phantom studies in which sources of different radioactivity concentration were placed within the chambers of the Octamouse. Next, potential effects of mass on the 18F-Fallypride binding potential (BPND) in the striatum were tested in groups of mice receiving 18F-Fallypride at 2 different specific activities (140 and 50 GBq/ mmol), with and without scatter correction. Finally, the relation-ship between BPND and injected dose of 18F-Fallypride (3.5–17 MBq/mouse) was tested. Results: Scatter correction improved the contrast between sources and air space within the Octa

  • Validation of the Octamouse for Simultaneous 18F-Fallypride Small-Animal PET Recordings from 8 Mice
    2016
    Co-Authors: Axel Rominger, Erik Mille, Franz Josef Gildehaus, Peter Bartenstein, Shanshan Zhang, Sebastian Nowak, Paul Cumming
    Abstract:

    Data collection in preclinical small-animal PET studies has been hindered by the small number of recordings typically obtained for a single radiosynthesis. Therefore, we tested procedures for obtaining 8 simultaneous small-animal PET recordings from the brains of 8 mice using an acrylic anesthesia distributor (the Octamouse), with the dopamine D2/3 ligand 18F-Fallypride serv-ing as a test substance for brain receptor imaging. Methods: The effect of scatter correction on the small-animal PET record-ings was first evaluated in phantom studies in which sources of different radioactivity concentration were placed within the chambers of the Octamouse. Next, potential effects of mass on the 18F-Fallypride binding potential (BPND) in the striatum were tested in groups of mice receiving 18F-Fallypride at 2 differ-ent specific activities (140 and 50 GBq/mmol), with and without scatter correction. Finally, the relationship between BPND an

Cristian Constantinescu - One of the best experts on this subject based on the ideXlab platform.

  • 18F-Fallypride PET of Pancreatic Islets: In Vitro and In Vivo Rodent Studies
    2016
    Co-Authors: Adriana Garcia, Norah Milne, Mohammad Mirbolooki, Min-liang Pan, Cristian Constantinescu, Ping H. Wang, Evegueni Sevrioukov, Jonathan Lakey, Jogeshwar Mukherjee
    Abstract:

    Islet cell loss in the pancreas results in diabetes. A noninvasive method that measures islet cell loss and also tracks the fate of transplanted islets would facilitate the development of novel therapeutics and improve the management of diabetes. We describe a novel dopamine D2/D3 receptor (D2/D3R)–based PET method to study islet cells in the rat pancreas and in islet cell transplantation. Methods: 18F-Fallypride binding to isolated rat islets and pancreas was evaluated in the absence and presence of the D2/D3R inhibitor haloperidol. After intravenous 18F-fall-ypride (28–37 MBq) administration, normal rats and rats pre-treated with haloperidol were imaged in a PET/CT scanner and subsequently studied ex vivo for 18F-Fallypride localization in the pancreas. A streptozotocin-treated diabetic rat model was used to study localization of 18F-Fallypride in the pancreas, in vitro and ex vivo. Rat islet cells were transplanted into th

  • Dopamine D3 receptor binding of (18)F-Fallypride: Evaluation using in vitro and in vivo PET imaging studies.
    Synapse (New York N.Y.), 2015
    Co-Authors: Jogeshwar Mukherjee, Cristian Constantinescu, Angela T. Hoang, Taleen Jerjian, Divya Majji, Min-liang Pan
    Abstract:

    Identification of dopamine D3 receptors (D3R) in vivo is important to understand several brain functions related to addiction. The goal of this work was to identify D3R binding of the dopamine D2 receptor (D2R)/D3R imaging agent, (18)F-Fallypride. Brain slices from male Sprague-Dawley rats (n = 6) and New Zealand White rabbits (n = 6) were incubated with (18)F-Fallypride and D3R selective agonist (R)-7-OH-DPAT (98-fold D3R selective). Rat slices were also treated with BP 897 (68-fold D3R selective partial agonist) and NGB 2904 (56-fold D3R selective antagonist). In vivo rat studies (n = 6) were done on Inveon PET using 18-37 MBq (18)F-Fallypride and drug-induced displacement by (R)-7-OH-DPAT, BP 897 and NGB 2904. PET/CT imaging of wild type (WT, n = 2) and D2R knock-out (KO, n = 2) mice were carried out with (18)F-Fallypride. (R)-7-OH-DPAT displaced binding of (18)F-Fallypride, both in vitro and in vivo. In vitro, at 10 nM (R)-7-OH-DPAT, (18)F-Fallypride binding in the rat ventral striatum (VST) and dorsal striatum (DST) and rabbit nucleus accumbens were reduced by ∼10-15%. At 10 μM (R)-7-OH-DPAT all regions in rat and rabbit were reduced by ≥85%. In vivo reductions for DST and VST before and after (R)-7-OH-DPAT were: low-dose (0.015 mg kg(-1)) DST -22%, VST -29%; high-dose (1.88 mg kg(-1)) DST -58%, VST -77%, suggesting D3R/D2R displacement. BP 897 and NGB 2904 competed with (18)F-Fallypride in vitro, but unlike BP 897, NGB 2904 did not displace (18)F-Fallypride in vivo. The D2R KO mice lacked (18)F-Fallypride binding in the DST. In summary, our findings suggest that up to 20% of (18)F-Fallypride may be bound to D3R sites in vivo.

  • spinal cord dopamine d2 d3 receptors in vivo and ex vivo imaging in the rat using 18f 11c Fallypride
    Nuclear Medicine and Biology, 2014
    Co-Authors: Jasmeet Kaur, Min-liang Pan, Cristian Constantinescu, Armen Khararjian, Robert Coleman, Jogeshwar Mukherjee
    Abstract:

    Abstract Objectives The spinal cord is known to be innervated with dopaminergic cells with catecholaminergic projections arising from the medulla and pons and dopaminergic transmission in the spinal cord is vital for sensory and motor function. Our goal was to evaluate and compare the imaging capability of dopamine D2/D3 receptors in the rat spinal cord using PET ligands 18 F-Fallypride and 11 C-Fallypride. Methods Male Sprague–Dawley rats were used in all in vitro and in vivo studies. Spinal cord and brain sections were used for in vitro autoradiography and ex vivo autoradiography. For in vivo studies animals received a 18 F-Fallypride scan or a 11 C-Fallypride PET scan. The spinal cord and the brain were then harvested, flash-frozen and imaged ex vivo. For in vivo analysis Logan plots with cerebellum as a reference was used to evaluate binding potentials (BP). Tissue ratios were used for ex vivo analysis. Drug effects were evaluated using clozapine, haloperidol and dopamine were evaluated on spinal cord sections in vitro. Results In vitro studies showed 18 F-Fallypride binding to superficial dorsal horn (SDH), dorsal horn (DH), ventral horn (VH) and the pars centralis (PC). In the cervical section, the greatest amount of binding appeared to be in the SDH. Ex vivo studies showed approximately 6% of 18 F-Fallypride in SDH compared to that observed in the striatum. In vivo analysis of both 18 F-Fallypride and 11 C-Fallypride in the spinal cord were comparable to that in the extrastriatal regions. Haloperidol and clozapine displaced more than 75% of the 18 F-Fallypride in spinal cord sections. Conclusions Our studies showed 18 F-Fallypride and 11 C-Fallypride binding in the spinal cord in vitro and in vivo. The binding pattern correlates well with the known distribution of dopamine D2/D3 receptors in the spinal cord.

  • Spinal cord dopamine D2/D3 receptors: in vivo and ex vivo imaging in the rat using 18F/11C-Fallypride
    Nuclear medicine and biology, 2014
    Co-Authors: Jasmeet Kaur, Min-liang Pan, Cristian Constantinescu, Armen Khararjian, Robert Coleman, Jogeshwar Mukherjee
    Abstract:

    Abstract Objectives The spinal cord is known to be innervated with dopaminergic cells with catecholaminergic projections arising from the medulla and pons and dopaminergic transmission in the spinal cord is vital for sensory and motor function. Our goal was to evaluate and compare the imaging capability of dopamine D2/D3 receptors in the rat spinal cord using PET ligands 18 F-Fallypride and 11 C-Fallypride. Methods Male Sprague–Dawley rats were used in all in vitro and in vivo studies. Spinal cord and brain sections were used for in vitro autoradiography and ex vivo autoradiography. For in vivo studies animals received a 18 F-Fallypride scan or a 11 C-Fallypride PET scan. The spinal cord and the brain were then harvested, flash-frozen and imaged ex vivo. For in vivo analysis Logan plots with cerebellum as a reference was used to evaluate binding potentials (BP). Tissue ratios were used for ex vivo analysis. Drug effects were evaluated using clozapine, haloperidol and dopamine were evaluated on spinal cord sections in vitro. Results In vitro studies showed 18 F-Fallypride binding to superficial dorsal horn (SDH), dorsal horn (DH), ventral horn (VH) and the pars centralis (PC). In the cervical section, the greatest amount of binding appeared to be in the SDH. Ex vivo studies showed approximately 6% of 18 F-Fallypride in SDH compared to that observed in the striatum. In vivo analysis of both 18 F-Fallypride and 11 C-Fallypride in the spinal cord were comparable to that in the extrastriatal regions. Haloperidol and clozapine displaced more than 75% of the 18 F-Fallypride in spinal cord sections. Conclusions Our studies showed 18 F-Fallypride and 11 C-Fallypride binding in the spinal cord in vitro and in vivo. The binding pattern correlates well with the known distribution of dopamine D2/D3 receptors in the spinal cord.

  • 18F-Fallypride PET/CT scanning in healthy and diabetic rodents
    The Journal of Nuclear Medicine, 2012
    Co-Authors: Adriana Garcia, Min-liang Pan, Cristian Constantinescu, Jogeshwar Mukherjee
    Abstract:

    2098 Objectives Many efforts have been made to discover a non-invasive method of imaging beta cells in the pancreas. Human and rodent islets express the Dopamine 2 receptor (D2R). Previous binding studies with the D2R/D3R tracer 18F- Fallypride have shown specific binding to islets in-vitro and to pancreas sections ex-vivo. Our goal was to extend these studies for in-vivo imaging of endogenous islets in healthy rodents and in a streptozotocin rodent model of diabetes. Methods Four (4) Fasted 8-wk-old male Sprague-Dawley rats (≈280 g) were administered 18F-Fallypride (50 MBq/Kg) by tail vein injection and imaged for 2 h in an Inveon PET scanner followed by high resolution CT for anatomical deliniation and attenuation correction. Rats were then administered streptozotocin at a dose of 55 mg/kg and classified as diabetic when non-fasting serum blood glucose levels rose above 350 mg/dL for 3 consecutive days. In vivo PET/CT was performed 4 days after establishing diabetes. At the end of the study, pancreata of diabetic rats were cryosectioned for immunostaining of insulin. Results Average specific binding ratios (SBR) in pancreas with respect to the erectile spinae muscle reference region was 4.86±0.48 in controls and 1.04±0.75 in diabetic rats. Percent decrease of 18F-Fallypride binding in diabetic rats was found to be 79%. Immunostaining of insulin of STZ-treated rat pancreas confirmed the destruction of islets. Conclusions PET/CT scans of diabetic rodents showed a markedly reduced level of 18F-Fallypride binding in pancreas as compared to controls. This reduction in binding paralleled the reduction in beta cells determined by immunostaining. 18F-Fallypride may be a useful diagnostic marker for evaluating T1DM, T2DM and related disorders of the pancreas

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  • Dopamine receptor density and white mater integrity: ^18F-Fallypride positron emission tomography and diffusion tensor imaging study in healthy and schizophrenia subjects
    Brain Imaging and Behavior, 2020
    Co-Authors: Semen A. Mitelman, Bradley T Christian, Bradley R Buchsbaum, Jogeshwar Mukherjee, Monte S. Buchsbaum, Brian M. Merrill, Douglas S Lehrer
    Abstract:

    Dopaminergic dysfunction and changes in white matter integrity are among the most replicated findings in schizophrenia. A modulating role of dopamine in myelin formation has been proposed in animal models and healthy human brain, but has not yet been systematically explored in schizophrenia. We used diffusion tensor imaging and ^18F-Fallypride positron emission tomography in 19 healthy and 25 schizophrenia subjects to assess the relationship between gray matter dopamine D_2/D_3 receptor density and white matter fractional anisotropy in each diagnostic group. AFNI regions of interest were acquired for 42 cortical Brodmann areas and subcortical gray matter structures as well as stereotaxically placed in representative white matter areas implicated in schizophrenia neuroimaging literature. Welch’s t-test with permutation-based p value adjustment was used to compare means of z-transformed correlations between fractional anisotropy and ^18F-Fallypride binding potentials in hypothesis-driven regions of interest in the diagnostic groups. Healthy subjects displayed an extensive pattern of predominantly negative correlations between ^18F-Fallypride binding across a range of cortical and subcortical gray matter regions and fractional anisotropy in rostral white matter regions (internal capsule, frontal lobe, anterior corpus callosum). These patterns were disrupted in subjects with schizophrenia, who displayed significantly weaker overall correlations as well as comparatively scant numbers of significant correlations with the internal capsule and frontal (but not temporal) white matter, especially for dopamine receptor density in thalamic nuclei. Dopamine D_2/D_3 receptor density and white matter integrity appear to be interrelated, and their decreases in schizophrenia may stem from hyperdopaminergia with dysregulation of dopaminergic impact on axonal myelination.

  • positive association between cerebral grey matter metabolism and dopamine d2 d3 receptor availability in healthy and schizophrenia subjects an 18f fluorodeoxyglucose and 18f Fallypride positron emission tomography study
    World Journal of Biological Psychiatry, 2020
    Co-Authors: Semen A. Mitelman, Bradley T Christian, Bradley R Buchsbaum, Jogeshwar Mukherjee, Monte S. Buchsbaum, Brian Merrill, Douglas S Lehrer
    Abstract:

    : Objectives: Overlapping decreases in extrastriatal dopamine D2/D3-receptor availability and glucose metabolism have been reported in subjects with schizophrenia. It remains unknown whether these findings are physiologically related or coincidental. Methods: To ascertain this, we used two consecutive 18F-fluorodeoxyglucose and 18F-Fallypride positron emission tomography scans in 19 healthy and 25 unmedicated schizophrenia subjects. Matrices of correlations between 18F-fluorodeoxyglucose uptake and 18F-Fallypride binding in voxels at the same xyz location and AFNI-generated regions of interest were evaluated in both diagnostic groups. Results:18F-fluorodeoxyglucose uptake and 18F-Fallypride binding potential were predominantly positively correlated across the striatal and extrastriatal grey matter in both healthy and schizophrenia subjects. In comparison to healthy subjects, significantly weaker correlations in subjects with schizophrenia were confirmed in the right cingulate gyrus and thalamus, including the mediodorsal, lateral dorsal, anterior, and midline nuclei. Schizophrenia subjects showed decreased D2/D3-receptor availability in the hypothalamus, mamillary bodies, thalamus and several thalamic nuclei, and increased glucose uptake in three lobules of the cerebellar vermis. Conclusions: Dopaminergic system may be involved in modulation of grey matter metabolism and neurometabolic coupling in both healthy human brain and psychopathology. Hyperdopaminergic state in untreated schizophrenia may at least partly account for the corresponding decreases in grey matter metabolism.

  • d2 d3 dopamine receptor binding with f 18 Fallypride correlates of executive function in medication naive patients with schizophrenia
    Schizophrenia Research, 2018
    Co-Authors: Bradley T Christian, Douglas S Lehrer, Monte S. Buchsbaum, Brian Merrill, Nora S. Vyas, Alex Decastro, Nicholas A. Doninger, Jogeshwar Mukherjee
    Abstract:

    Converging evidence indicates that the prefrontal cortex is critically involved in executive control and that executive dysfunction is implicated in schizophrenia. Reduced dopamine D2/D3 receptor binding potential has been reported in schizophrenia, and the correlations with neuropsychological test scores have been positive and negative for different tasks. The aim of this study was to examine the relation between dopamine D2/D3 receptor levels with frontal and temporal neurocognitive performance in schizophrenia. Resting-state 18F-Fallypride positron emission tomography was performed on 20 medication-naive and 5 previously medicated for brief earlier periods patients with schizophrenia and 19 age- and sex-matched healthy volunteers. Striatal and extra-striatal dopamine D2/D3 receptor levels were quantified as binding potential using Fallypride imaging. Magnetic resonance images in standard Talairach position and segmented into gray and white matter were co-registered to the Fallypride images, and the AFNI stereotaxic atlas was applied. Two neuropsychological tasks known to activate frontal and temporal lobe function were chosen, specifically the Wisconsin Card Sorting Test (WCST) and the California Verbal Learning Test (CVLT). Images of the correlation coefficient between Fallypride binding and WCST and CVLT performance showed a negative correlation in contrast to positive correlations in healthy volunteers. The results of this study demonstrate that lower Fallypride binding potential in patients with schizophrenia may be associated with better performance. Our findings are consistent with previous studies that failed to find cognitive improvements with typical dopamine-blocking medications.

  • D2/D3 dopamine receptor binding with [F-18]Fallypride correlates of executive function in medication-naïve patients with schizophrenia.
    Schizophrenia research, 2017
    Co-Authors: Nora S. Vyas, Bradley T Christian, Douglas S Lehrer, Monte S. Buchsbaum, Brian Merrill, Alex Decastro, Nicholas A. Doninger, Jogeshwar Mukherjee
    Abstract:

    Converging evidence indicates that the prefrontal cortex is critically involved in executive control and that executive dysfunction is implicated in schizophrenia. Reduced dopamine D2/D3 receptor binding potential has been reported in schizophrenia, and the correlations with neuropsychological test scores have been positive and negative for different tasks. The aim of this study was to examine the relation between dopamine D2/D3 receptor levels with frontal and temporal neurocognitive performance in schizophrenia. Resting-state 18F-Fallypride positron emission tomography was performed on 20 medication-naive and 5 previously medicated for brief earlier periods patients with schizophrenia and 19 age- and sex-matched healthy volunteers. Striatal and extra-striatal dopamine D2/D3 receptor levels were quantified as binding potential using Fallypride imaging. Magnetic resonance images in standard Talairach position and segmented into gray and white matter were co-registered to the Fallypride images, and the AFNI stereotaxic atlas was applied. Two neuropsychological tasks known to activate frontal and temporal lobe function were chosen, specifically the Wisconsin Card Sorting Test (WCST) and the California Verbal Learning Test (CVLT). Images of the correlation coefficient between Fallypride binding and WCST and CVLT performance showed a negative correlation in contrast to positive correlations in healthy volunteers. The results of this study demonstrate that lower Fallypride binding potential in patients with schizophrenia may be associated with better performance. Our findings are consistent with previous studies that failed to find cognitive improvements with typical dopamine-blocking medications.

  • 79 d2 d3 dopamine receptor binding with f 18 Fallypride correlates of executive function in medication naive patients with schizophrenia
    Schizophrenia Bulletin, 2017
    Co-Authors: Monte S. Buchsbaum, Bradley T Christian, Douglas S Lehrer, Nora S. Vyas, Brian Merill, Alex Decastro, Nicholas Donninger, Jogeshwar Mukherjee
    Abstract:

    Abstract Background: Converging evidence indicates that the prefrontal cortex is critically involved in executive control and that executive dysfunction is implicated in schizophrenia. Reduced dopamine D2/D3 receptor binding potential has been reported in schizophrenia, and the correlations with neuropsychological test scores have been positive and negative for different tasks. The aim of this study was to examine the relation between dopamine D2/D3 receptor levels with frontal and temporal neurocognitive performance in schizophrenia. Methods: Resting-state 18F-Fallypride positron emission tomography was performed on 20 medication-naive and 5 previously medicated for brief earlier periods patients with schizophrenia and 19 age- and sex-matched normal controls. Striatal and extra-striatal dopamine D2/D3 receptor levels were quantified as binding potential using Fallypride imaging. Magnetic resonance images in standard Talairach position and segmented into gray and white matter were co-registered to the Fallypride images, and the AFNI stereotaxic atlas was applied. Two neuropsychological tasks known to activate frontal and temporal lobe function were chosen, specifically the Wisconsin Card Sorting Test (WCST) and the California Verbal Learning Test (CVLT). Results: Images of the correlation coefficient between Fallypride binding and WCST and CVLT performance showed a negative correlation in contrast to positive correlations in healthy volunteers. Prefrontal Brodmann area 10 and striatal areas showed the greatest differences. Heat maps of correlation patterns of Fallypride binding potential and neuropsychological performance were obtained. Differences in correlation patterns between healthy volunteers and patients were confirmed with Monte Carlo permutation analysis. Correlation coefficient histograms also showed significant differences in shape. Conclusion: The results of this study demonstrate that lower Fallypride binding potential in patients with schizophrenia may be associated with better performance and consistent with previous studies that failed to find cognitive improvement with typical dopamine-blocking medications.