Header

UZH-Logo

Maintenance Infos

Cannabinoid receptor type 2 (CB2) as one of the candidate genes in human carotid plaque imaging: evaluation of the novel radiotracer [ 11 c]rs-016 targeting CB2 in atherosclerosis


Meletta, Romana; Slavik, Roger; Mu, Linjing; Rancic, Zoran; Borel, Nicole; Schibli, Roger; Ametamey, Simon M; Krämer, Stefanie D; Müller Herde, Adrienne (2017). Cannabinoid receptor type 2 (CB2) as one of the candidate genes in human carotid plaque imaging: evaluation of the novel radiotracer [ 11 c]rs-016 targeting CB2 in atherosclerosis. Nuclear medicine and biology, 47:31-43.

Abstract

Introduction: Endarterectomized human atherosclerotic plaques are a valuable basis for gene expression studies
to disclose novel imaging biomarkers and therapeutic targets, such as the cannabinoid receptor type 2 (CB2). In
this work, CB2 is expressed on activated immune cells, which are abundant in inflamed plaques. We evaluated
the CB2-specific radiotracer [11C]RS-016 for imaging vascular inflammation in human and mouse atherosclerotic
lesions.
Methods: The differential gene expression of microscopically classified human carotid plaques was evaluated
using quantitative polymerase chain reaction. In addition, CB2 expression levels in human plaques were
investigated by in vitro autoradiography. As an appropriate animal model we used apolipoprotein E knockout
mice (ApoE KO) with shear stress-induced atherosclerosis to evaluate CB2 levels in vivo. Positron emission
tomography (PET) was performed with both the CB2 radioligand [11C]RS-016 and the metabolic radiotracer
[18F]fluorodeoxyglucose ([18F]FDG) at various time points. Retrospectively, carotids were dissected for
histopathology and gene expression analysis.
Results: We identified 28 human genes differentially expressed in atherosclerotic plaques compared to normal
arteries of which 12 were upregulated preferentially in vulnerable plaques. The latter group included members
of matrix metalloproteinase family and the T-lymphocyte activation antigens CD80 and CD86. CB2 was
upregulated by 2-fold in human atherosclerotic plaques correlating with CD68 expression levels. Specific
in vitro binding of [11C]RS-016 was predominantly observed to plaques. In vivo PET imaging of ApoE KO mice
revealed accumulation of [11C]RS-016 and [18F]FDGin atherosclerotic plaques. Development of advanced plaques
with elevated CB2 and CD68 levels were found in vitro in ApoE KO mice resembling human vulnerable plaques.
Conclusion: We identified human genes associated with plaque vulnerability, which potentially could serve as
novel imaging or therapeutic targets. The CB2-specific radiotracer [11C]RS-016 detected human plaques by
in vitro autoradiography and accumulated in vivo in plaques of ApoE KO mice, however not exclusively in
vulnerable plaques.

Abstract

Introduction: Endarterectomized human atherosclerotic plaques are a valuable basis for gene expression studies
to disclose novel imaging biomarkers and therapeutic targets, such as the cannabinoid receptor type 2 (CB2). In
this work, CB2 is expressed on activated immune cells, which are abundant in inflamed plaques. We evaluated
the CB2-specific radiotracer [11C]RS-016 for imaging vascular inflammation in human and mouse atherosclerotic
lesions.
Methods: The differential gene expression of microscopically classified human carotid plaques was evaluated
using quantitative polymerase chain reaction. In addition, CB2 expression levels in human plaques were
investigated by in vitro autoradiography. As an appropriate animal model we used apolipoprotein E knockout
mice (ApoE KO) with shear stress-induced atherosclerosis to evaluate CB2 levels in vivo. Positron emission
tomography (PET) was performed with both the CB2 radioligand [11C]RS-016 and the metabolic radiotracer
[18F]fluorodeoxyglucose ([18F]FDG) at various time points. Retrospectively, carotids were dissected for
histopathology and gene expression analysis.
Results: We identified 28 human genes differentially expressed in atherosclerotic plaques compared to normal
arteries of which 12 were upregulated preferentially in vulnerable plaques. The latter group included members
of matrix metalloproteinase family and the T-lymphocyte activation antigens CD80 and CD86. CB2 was
upregulated by 2-fold in human atherosclerotic plaques correlating with CD68 expression levels. Specific
in vitro binding of [11C]RS-016 was predominantly observed to plaques. In vivo PET imaging of ApoE KO mice
revealed accumulation of [11C]RS-016 and [18F]FDGin atherosclerotic plaques. Development of advanced plaques
with elevated CB2 and CD68 levels were found in vitro in ApoE KO mice resembling human vulnerable plaques.
Conclusion: We identified human genes associated with plaque vulnerability, which potentially could serve as
novel imaging or therapeutic targets. The CB2-specific radiotracer [11C]RS-016 detected human plaques by
in vitro autoradiography and accumulated in vivo in plaques of ApoE KO mice, however not exclusively in
vulnerable plaques.

Statistics

Altmetrics

Downloads

1 download since deposited on 06 Jul 2017
1 download since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Pathology
Dewey Decimal Classification:570 Life sciences; biology
Uncontrolled Keywords:ApoE KO; Cannabinoid receptor type 2; Gene expression; Plaque inflammation; Positron emission tomography; Shear stress
Language:English
Date:2017
Deposited On:06 Jul 2017 10:06
Last Modified:06 Jul 2017 10:06
Publisher:Elsevier
ISSN:0969-8051
Publisher DOI:https://doi.org/10.1016/j.nucmedbio.2017.01.001
PubMed ID:28104528

Download

Preview Icon on Download
Content: Published Version
Language: English
Filetype: PDF - Registered users only
Size: 2MB
View at publisher