Non-Invasive Imaging of the Type 2 Cannabinoid Receptor, Focus on Positron Emission Tomography

Evens, Nele; Bormans, Guy

doi:10.2174/156802610793176819

Cited by 34 publications

(34 citation statements)

References 128 publications

(179 reference statements)

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“…18 Despite the advantages of high sensitivity and deep tissue penetration, PET has many limitations, such as relatively low resolution, narrow time window, high instrument cost, and injection of radioactive agents. Optical imaging, however, serves as an alternative low-cost approach with relatively high sensitivity and resolution.…”

Section: Introductionmentioning

confidence: 99%

In Vivo Type 2 Cannabinoid Receptor-Targeted Tumor Optical Imaging Using a Near Infrared Fluorescent Probe

2013

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The type 2 cannabinoid receptor (CB2R) plays a vital role in carcinogenesis and progression and is emerging as a therapeutic target for cancers. However, the exact role of CB2R in cancer progression and therapy remains unclear. This has driven the increasing efforts to study CB2R and cancers using molecular imaging tools. In addition, many types of cancers overexpress CB2R, and the expression levels of CB2R appear to be associated with tumor aggressiveness. Such upregulation of the receptor in cancer cells provides opportunities for CB2R-targeted imaging with high contrast and for therapy with low side effects. In the present study, we report the first in vivo tumor-targeted optical imaging using a novel CB2R-targeted near-infrared probe. In vitro cell fluorescent imaging and a competitive binding assay indicated specific binding of NIR760-mbc94 to CB2R in CB2-mid delayed brain tumor (DBT) cells. NIR760-mbc94 also preferentially labeled CB2-mid DBT tumors in vivo, with a 3.7-fold tumor-to-normal contrast enhancement at 72 h postinjection, whereas the fluorescence signal from the tumors of the mice treated with NIR760 free dye was nearly at the background level at the same time point. SR144528, a CB2R competitor, significantly inhibited tumor uptake of NIR760-mbc94, indicating that NIR760-mbc94 binds to CB2R specifically. In summary, NIR760-mbc94 specifically binds to CB2R in vitro and in vivo and appears to be a promising molecular tool that may have great potential for use in diagnostic imaging of CB2R-positive cancers and therapeutic monitoring as well as in elucidating the role of CB2R in cancer progression and therapy.

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Section: Introductionmentioning

confidence: 99%

In Vivo Type 2 Cannabinoid Receptor-Targeted Tumor Optical Imaging Using a Near Infrared Fluorescent Probe

2013

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“…In this study, hSSTR2 was chosen as the reporter over others such as the sodium iodide symporter (Chung, 2002), herpes simplex virus 1 thymidine kinase (Gambhir et al, 2003) and CB 2 R (Evens & Bormans, 2010) because the radiolabelled ligand [ 64 Cu]CB-TE1A1P-Y3-TATE has high binding affinity to SSTR2 (K d 51.8 + 0.5 nM), and a favourable pharmacokinetics with fast targeting and rapid blood clearance resulting in relatively low background (Guo et al, 2012). SSTR2 is also expressed at much lower levels in certain tissues, pituitary gland, pancreas and adrenals (Patel, 1999), which does not significantly interfere with imaging viral infection (Fig.…”

Section: Discussionmentioning

confidence: 99%

Visualization and quantification of simian immunodeficiency virus-infected cells using non-invasive molecular imaging

Song

Cai

White

et al. 2015

Journal of General Virology

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In vivo imaging can provide real-time information and three-dimensional (3D) non-invasive images of deep tissues and organs, including the brain, whilst allowing longitudinal observation of the same animals, thus eliminating potential variation between subjects. Current in vivo imaging technologies, such as magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT) and bioluminescence imaging (BLI), can be used to pinpoint the spatial location of target cells, which is urgently needed for revealing human immunodeficiency virus (HIV) dissemination in real-time and HIV-1 reservoirs during suppressive antiretroviral therapy (ART). To demonstrate that in vivo imaging can be used to visualize and quantify simian immunodeficiency virus (SIV)-transduced cells, we genetically engineered SIV to carry different imaging reporters. Based on the expression of the reporter genes, we could visualize and quantify the SIV-transduced cells via vesicular stomatitis virus glycoprotein pseudotyping in a mouse model using BLI, PET-CT or MRI. We also engineered a chimeric EcoSIV for in vivo infection study. Our results demonstrated that BLI is sensitive enough to detect as few as five single cells transduced with virus, whilst PET-CT can provide 3D images of the spatial location of as few as 10 000 SIV-infected cells. We also demonstrated that MRI can provide images with high spatial resolution in a 3D anatomical context to distinguish a small population of SIV-transduced cells. The in vivo imaging platform described here can potentially serve as a powerful tool to visualize lentiviral infection, including when and where viraemia rebounds, and how reservoirs are formed and maintained during latency or suppressive ART.

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“…CB 2 R is expressed at a much lower level in the normal brain tissue compared to CB 1 R. Under pathological conditions, especially immune-mediated pathologies, up-regulation of CB 2 R is found on activated microglia, the resident immune cells in the CNS 72. Three major groups of CB 2 R ligands can be labeled with radioisotopes for PET, including pyrazole derivatives, indole derivatives, and quinoline derivatives 73. For 11 C-labeling of pyrazole derivatives, a boron precursor was first synthesized and later reacted with 11 C-methyl iodide via a Suzuki coupling 74.…”

Section: Biomarkers For Inflammation Imagingmentioning

confidence: 99%

PET Imaging of Inflammation Biomarkers

Wu¹,

Li²,

Niu³

et al. 2013

Theranostics

164

114

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Inflammation plays a significant role in many disease processes. Development in molecular imaging in recent years provides new insight into the diagnosis and treatment evaluation of various inflammatory diseases and diseases involving inflammatory process. Positron emission tomography using 18F-FDG has been successfully applied in clinical oncology and neurology and in the inflammation realm. In addition to glucose metabolism, a variety of targets for inflammation imaging are being discovered and utilized, some of which are considered superior to FDG for imaging inflammation. This review summarizes the potential inflammation imaging targets and corresponding PET tracers, and the applications of PET in major inflammatory diseases and tumor associated inflammation. Also, the current attempt in differentiating inflammation from tumor using PET is also discussed.

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Non-Invasive Imaging of the Type 2 Cannabinoid Receptor, Focus on Positron Emission Tomography

Cited by 34 publications

References 128 publications

In Vivo Type 2 Cannabinoid Receptor-Targeted Tumor Optical Imaging Using a Near Infrared Fluorescent Probe

In Vivo Type 2 Cannabinoid Receptor-Targeted Tumor Optical Imaging Using a Near Infrared Fluorescent Probe

Visualization and quantification of simian immunodeficiency virus-infected cells using non-invasive molecular imaging

PET Imaging of Inflammation Biomarkers

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