Quantification of cerebral cannabinoid receptors subtype 1 (CB1) in healthy subjects and schizophrenia by the novel PET radioligand [11C]OMAR
Several studies have examined the link between the cannabinoid CB1 receptor and several neuropsychiatric illnesses, including schizophrenia. As such, there is a need for in vivo imaging tracers so that the relationship between CB1 and schizophrenia (SZ) can be further studied. In this paper, we pres...
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| Published in | NeuroImage (Orlando, Fla.) Vol. 52; no. 4; pp. 1505 - 1513 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.10.2010
Elsevier Limited |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Several studies have examined the link between the cannabinoid CB1 receptor and several neuropsychiatric illnesses, including schizophrenia. As such, there is a need for in vivo imaging tracers so that the relationship between CB1 and schizophrenia (SZ) can be further studied. In this paper, we present our first human studies in both healthy control patients and patients with schizophrenia using the novel PET tracer, [11C]OMAR (JHU75528), we have shown its utility as a tracer for imaging human CB1 receptors and to investigate normal aging and the differences in the cannabinoid system of healthy controls versus patients with schizophrenia. A total of ten healthy controls and nine patients with schizophrenia were included and studied with high specific activity [11C]OMAR. The CB1 binding (expressed as the distribution volume; VT) was highest in the globus pallidus and the cortex in both controls and patients with schizophrenia. Controls showed a correlation with the known distribution of CB1 and decline of [11C]OMAR binding with age, most significantly in the globus pallidus. Overall, we observed elevated mean binding in patients with schizophrenia across all regions studied, and this increase was statistically significant in the pons (p<0.05), by the Students t-test. When we ran a regression of the control subjects VT values with age and then compared the patient data to 95% prediction limits of the linear regression, three patients fell completely outside for the globus pallidus, and in all other regions there were at least 1–3 patients outside of the prediction intervals. There was no statistically significant correlations between PET measures and the individual Brief Psychiatry Rating Score (BPRS) subscores (r=0.49), but there was a significant correlation between VT and the ratio of the BPRS psychosis to withdrawal score in the frontal lobe (r=0.60), and middle and posterior cingulate regions (r=0.71 and r=0.79 respectively). In conclusion, we found that [11C] OMAR can image human CB1 receptors in normal aging and schizophrenia. In addition, our initial data in subjects with schizophrenia seem to suggest an association of elevated binding specific brain regions and symptoms of the disease. |
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| AbstractList | Several studies have examined the link between the cannabinoid CB1 receptor and several neuropsychiatric illnesses, including schizophrenia. As such, there is a need for in vivo imaging tracers so that the relationship between CB1 and schizophrenia (SZ) can be further studied. In this paper, we present our first human studies in both healthy control patients and patients with schizophrenia using the novel PET tracer, [
11
C]OMAR (JHU 75528), we have shown its utility as a tracer for imaging human CB1 receptors and to investigate normal aging and the differences in the cannabinoid system of healthy controls versus patients with schizophrenia. A total of ten healthy controls and nine patients with schizophrenia were included and studied with high specific activity [
11
C]OMAR. The CB1 binding (expressed as the distribution volume; V
T
) was highest in the globus pallidus and the cortex in both controls and patients with schizophrenia. Controls showed a correlation with the known distribution of CB1 and decline of [
11
C]OMAR binding with age, most significantly in the globus pallidus. Overall, we observed elevated mean binding in patients with schizophrenia across all regions studied, and this increase was statistically significant in the pons (p<0.05), by the students t-test. When we ran a regression of the control subjects V
T
values with age and then compared the patient data to 95% prediction limits of the linear regression, three patients fell completely outside for the globus pallidus, and in all other regions there were at least 1-3 patients outside of the prediction intervals. There was no statistically significant correlations between PET measures and the individual Brief Psychiatry Rating Score (BPRS) subscores, but there was a significant correlation between V
T
and the ratio of the BPRS psychosis to withdrawal score in the frontal lobe (r=0.49), (r=0.60), and middle and posterior cingulate regions (r=0.71 and r=0.79 respectively). In conclusion, we found that [
11
C] OMAR can image human CB1 receptors in normal aging and schizophrenia. In additon, our initial data in subjects with schizophrenia seem to suggest an association of elevated binding specific brain regions and symptoms of the disease. Several studies have examined the link between the cannabinoid CB1 receptor and several neuropsychiatric illnesses, including schizophrenia. As such, there is a need for in vivo imaging tracers so that the relationship between CB1 and schizophrenia (SZ) can be further studied. In this paper, we present our first human studies in both healthy control patients and patients with schizophrenia using the novel PET tracer, [11C]OMAR (JHU75528), we have shown its utility as a tracer for imaging human CB1 receptors and to investigate normal aging and the differences in the cannabinoid system of healthy controls versus patients with schizophrenia. A total of ten healthy controls and nine patients with schizophrenia were included and studied with high specific activity [11C]OMAR. The CB1 binding (expressed as the distribution volume; VT) was highest in the globus pallidus and the cortex in both controls and patients with schizophrenia. Controls showed a correlation with the known distribution of CB1 and decline of [11C]OMAR binding with age, most significantly in the globus pallidus. Overall, we observed elevated mean binding in patients with schizophrenia across all regions studied, and this increase was statistically significant in the pons (p<0.05), by the Students t-test. When we ran a regression of the control subjects VT values with age and then compared the patient data to 95% prediction limits of the linear regression, three patients fell completely outside for the globus pallidus, and in all other regions there were at least 1–3 patients outside of the prediction intervals. There was no statistically significant correlations between PET measures and the individual Brief Psychiatry Rating Score (BPRS) subscores (r=0.49), but there was a significant correlation between VT and the ratio of the BPRS psychosis to withdrawal score in the frontal lobe (r=0.60), and middle and posterior cingulate regions (r=0.71 and r=0.79 respectively). In conclusion, we found that [11C] OMAR can image human CB1 receptors in normal aging and schizophrenia. In addition, our initial data in subjects with schizophrenia seem to suggest an association of elevated binding specific brain regions and symptoms of the disease. Several studies have examined the link between the cannabinoid CB1 receptor and several neuropsychiatric illnesses, including schizophrenia. As such, there is a need for in vivo imaging tracers so that the relationship between CB1 and schizophrenia (SZ) can be further studied. In this paper, we present our first human studies in both healthy control patients and patients with schizophrenia using the novel PET tracer, [(11)C]OMAR (JHU75528), we have shown its utility as a tracer for imaging human CB1 receptors and to investigate normal aging and the differences in the cannabinoid system of healthy controls versus patients with schizophrenia. A total of ten healthy controls and nine patients with schizophrenia were included and studied with high specific activity [(11)C]OMAR. The CB1 binding (expressed as the distribution volume; V(T)) was highest in the globus pallidus and the cortex in both controls and patients with schizophrenia. Controls showed a correlation with the known distribution of CB1 and decline of [(11)C]OMAR binding with age, most significantly in the globus pallidus. Overall, we observed elevated mean binding in patients with schizophrenia across all regions studied, and this increase was statistically significant in the pons (p<0.05), by the Students t-test. When we ran a regression of the control subjects V(T) values with age and then compared the patient data to 95% prediction limits of the linear regression, three patients fell completely outside for the globus pallidus, and in all other regions there were at least 1-3 patients outside of the prediction intervals. There was no statistically significant correlations between PET measures and the individual Brief Psychiatry Rating Score (BPRS) subscores (r=0.49), but there was a significant correlation between V(T) and the ratio of the BPRS psychosis to withdrawal score in the frontal lobe (r=0.60), and middle and posterior cingulate regions (r=0.71 and r=0.79 respectively). In conclusion, we found that [(11)C] OMAR can image human CB1 receptors in normal aging and schizophrenia. In addition, our initial data in subjects with schizophrenia seem to suggest an association of elevated binding specific brain regions and symptoms of the disease. Several studies have examined the link between the cannabinoid CB1 receptor and several neuropsychiatric illnesses, including schizophrenia. As such, there is a need for in vivo imaging tracers so that the relationship between CB1 and schizophrenia (SZ) can be further studied. In this paper, we present our first human studies in both healthy control patients and patients with schizophrenia using the novel PET tracer, [ super(11)C]OMAR (JHU75528), we have shown its utility as a tracer for imaging human CB1 receptors and to investigate normal aging and the differences in the cannabinoid system of healthy controls versus patients with schizophrenia. A total of ten healthy controls and nine patients with schizophrenia were included and studied with high specific activity [ super(11)C]OMAR. The CB1 binding (expressed as the distribution volume; V sub(T)) was highest in the globus pallidus and the cortex in both controls and patients with schizophrenia. Controls showed a correlation with the known distribution of CB1 and decline of [ super(11)C]OMAR binding with age, most significantly in the globus pallidus. Overall, we observed elevated mean binding in patients with schizophrenia across all regions studied, and this increase was statistically significant in the pons (p < 0.05), by the Students t-test. When we ran a regression of the control subjects V sub(T) values with age and then compared the patient data to 95% prediction limits of the linear regression, three patients fell completely outside for the globus pallidus, and in all other regions there were at least 1-3 patients outside of the prediction intervals. There was no statistically significant correlations between PET measures and the individual Brief Psychiatry Rating Score (BPRS) subscores (r = 0.49), but there was a significant correlation between V sub(T) and the ratio of the BPRS psychosis to withdrawal score in the frontal lobe (r = 0.60), and middle and posterior cingulate regions (r = 0.71 and r = 0.79 respectively). In conclusion, we found that [ super(11)C] OMAR can image human CB1 receptors in normal aging and schizophrenia. In addition, our initial data in subjects with schizophrenia seem to suggest an association of elevated binding specific brain regions and symptoms of the disease. Several studies have examined the link between the cannabinoid CB1 receptor and several neuropsychiatric illnesses, including schizophrenia. As such, there is a need for in vivo imaging tracers so that the relationship between CB1 and schizophrenia (SZ) can be further studied. In this paper, we present our first human studies in both healthy control patients and patients with schizophrenia using the novel PET tracer, [11C]OMAR (JHU75528), we have shown its utility as a tracer for imaging human CB1 receptors and to investigate normal aging and the differences in the cannabinoid system of healthy controls versus patients with schizophrenia. A total of ten healthy controls and nine patients with schizophrenia were included and studied with high specific activity [11C]OMAR. The CB1 binding (expressed as the distribution volume;VT) was highest in the globus pallidus and the cortex in both controls and patients with schizophrenia. Controls showed a correlation with the known distribution of CB1 and decline of [11C]OMAR binding with age, most significantly in the globus pallidus. Overall, we observed elevated mean binding in patients with schizophrenia across all regions studied, and this increase was statistically significant in the pons (p<0.05), by the Studentst-test. When we ran a regression of the control subjectsVTvalues with age and then compared the patient data to 95% prediction limits of the linear regression, three patients fell completely outside for the globus pallidus, and in all other regions there were at least 1-3 patients outside of the prediction intervals. There was no statistically significant correlations between PET measures and the individual Brief Psychiatry Rating Score (BPRS) subscores (r=0.49), but there was a significant correlation betweenVTand the ratio of the BPRS psychosis to withdrawal score in the frontal lobe (r=0.60), and middle and posterior cingulate regions (r=0.71 andr=0.79 respectively). In conclusion, we found that [11C] OMAR can image human CB1 receptors in normal aging and schizophrenia. In addition, our initial data in subjects with schizophrenia seem to suggest an association of elevated binding specific brain regions and symptoms of the disease. |
| Author | Rahmim, Arman Horti, Andrew G. Wong, Dean F. Raymont, Vanessa Brasic, James Ravert, Hayden T. Kuwabara, Hiroto Guevara, Maria Nandi, Ayon Dannals, Robert F. Ming, Jeffrey E. Roy, Christine Cascella, Nicola Ye, Weiguo Grachev, Igor |
| AuthorAffiliation | Clinical and Exploratory Pharmacology, Sanofi-aventis Research and Development, Bridgewater, NJ, Malvern, PA, and Paris, France X Radiology, Johns Hopkins University, Baltimore, MD o Psychiatry, Johns Hopkins University, Baltimore, MD Neuroscience, Johns Hopkins University, Baltimore, MD |
| AuthorAffiliation_xml | – name: o Psychiatry, Johns Hopkins University, Baltimore, MD – name: X Radiology, Johns Hopkins University, Baltimore, MD – name: Clinical and Exploratory Pharmacology, Sanofi-aventis Research and Development, Bridgewater, NJ, Malvern, PA, and Paris, France – name: Neuroscience, Johns Hopkins University, Baltimore, MD |
| Author_xml | – sequence: 1 givenname: Dean F. surname: Wong fullname: Wong, Dean F. email: dfwong@jhmi.edu organization: Radiology, Johns Hopkins University, Baltimore, MD, USA – sequence: 2 givenname: Hiroto surname: Kuwabara fullname: Kuwabara, Hiroto organization: Radiology, Johns Hopkins University, Baltimore, MD, USA – sequence: 3 givenname: Andrew G. surname: Horti fullname: Horti, Andrew G. organization: Radiology, Johns Hopkins University, Baltimore, MD, USA – sequence: 4 givenname: Vanessa surname: Raymont fullname: Raymont, Vanessa organization: Radiology, Johns Hopkins University, Baltimore, MD, USA – sequence: 5 givenname: James surname: Brasic fullname: Brasic, James organization: Radiology, Johns Hopkins University, Baltimore, MD, USA – sequence: 6 givenname: Maria surname: Guevara fullname: Guevara, Maria organization: Radiology, Johns Hopkins University, Baltimore, MD, USA – sequence: 7 givenname: Weiguo surname: Ye fullname: Ye, Weiguo organization: Radiology, Johns Hopkins University, Baltimore, MD, USA – sequence: 8 givenname: Robert F. surname: Dannals fullname: Dannals, Robert F. organization: Radiology, Johns Hopkins University, Baltimore, MD, USA – sequence: 9 givenname: Hayden T. surname: Ravert fullname: Ravert, Hayden T. organization: Radiology, Johns Hopkins University, Baltimore, MD, USA – sequence: 10 givenname: Ayon surname: Nandi fullname: Nandi, Ayon organization: Radiology, Johns Hopkins University, Baltimore, MD, USA – sequence: 11 givenname: Arman surname: Rahmim fullname: Rahmim, Arman organization: Radiology, Johns Hopkins University, Baltimore, MD, USA – sequence: 12 givenname: Jeffrey E. surname: Ming fullname: Ming, Jeffrey E. organization: Clinical and Exploratory Pharmacology, Sanofi-aventis Research and Development, Malvern, PA, USA – sequence: 13 givenname: Igor surname: Grachev fullname: Grachev, Igor organization: Clinical and Exploratory Pharmacology, Sanofi-aventis Research and Development, Bridgewater, NJ, USA – sequence: 14 givenname: Christine surname: Roy fullname: Roy, Christine organization: Clinical and Exploratory Pharmacology, Sanofi-aventis Research and Development, Paris, France – sequence: 15 givenname: Nicola surname: Cascella fullname: Cascella, Nicola organization: Psychiatry, Johns Hopkins University, Baltimore, MD, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/20406692$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | 2010 Elsevier Inc. Copyright 2010 Elsevier Inc. All rights reserved. Copyright Elsevier Limited Oct 1, 2010 |
| Copyright_xml | – notice: 2010 Elsevier Inc. – notice: Copyright 2010 Elsevier Inc. All rights reserved. – notice: Copyright Elsevier Limited Oct 1, 2010 |
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| DOI | 10.1016/j.neuroimage.2010.04.034 |
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| Title | Quantification of cerebral cannabinoid receptors subtype 1 (CB1) in healthy subjects and schizophrenia by the novel PET radioligand [11C]OMAR |
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