PET Imaging of the Endocannabinoid System

Terry, Garth E.; Raymont, Vanessa; Horti, Andrew G.

doi:10.1007/978-3-030-53176-8_12

Cited by 3 publications

(10 citation statements)

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“…The development of novel potent and selective CB2R ligands is supported by computer-based docking studies and accelerated by the recently reported crystal structure of the receptor [ 41 ]. The non-invasive imaging of CB2R with positron emission tomography (PET) is of great interest, as demonstrated by the large number of positron-emitting radioligands developed over the past years [ 42 , 43 , 44 , 45 , 46 ].…”

Section: Introductionmentioning

confidence: 99%

Development of [18F]LU14 for PET Imaging of Cannabinoid Receptor Type 2 in the Brain

Teodoro

Gündel

Deuther‐Conrad

et al. 2021

IJMS

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Cannabinoid receptors type 2 (CB2R) represent an attractive therapeutic target for neurodegenerative diseases and cancer. Aiming at the development of a positron emission tomography (PET) radiotracer to monitor receptor density and/or occupancy during a CB2R-tailored therapy, we herein describe the radiosynthesis of cis-[18F]1-(4-fluorobutyl-N-((1s,4s)-4-methylcyclohexyl)-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxamide ([18F]LU14) starting from the corresponding mesylate precursor. The first biological evaluation revealed that [18F]LU14 is a highly affine CB2R radioligand with >80% intact tracer in the brain at 30 min p.i. Its further evaluation by PET in a well-established rat model of CB2R overexpression demonstrated its ability to selectively image the CB2R in the brain and its potential as a tracer to further investigate disease-related changes in CB2R expression.

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Section: Introductionmentioning

confidence: 99%

Development of [18F]LU14 for PET Imaging of Cannabinoid Receptor Type 2 in the Brain

Teodoro

Gündel

Deuther‐Conrad

et al. 2021

IJMS

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“…A number of PET radioligands were developed for CB2R to date and excellently summed-up in several recent reviews, ,, with the most recent CB2R radioligands depicted in Figure . Compound [ 18 F]DM102 was reported by Modemann and co-workers and proved by autoradiography with spleen tissue to bind to CB2R .…”

Section: Introductionmentioning

confidence: 99%

“…26 Given the low level of expression of CB2R along with the high level of CB1R under physiological conditions, for the neuroimaging of CB2R with PET, a radioligand binding to CB2R with high affinity with K D in low nanomolar range and high selectivity versus CB1R is needed. 22 A number of PET radioligands were developed for CB2R to date and excellently summed-up in several recent reviews, 22,23,27 with the most recent CB2R radioligands depicted in Figure 1. Compound [ 18 F]DM102 was reported by Modemann and coworkers and proved by autoradiography with spleen tissue to bind to CB2R.…”

Section: ■ Introductionmentioning

confidence: 99%

Synthesis, Structure–Activity Relationships, Radiofluorination, and Biological Evaluation of [¹⁸F]RM365, a Novel Radioligand for Imaging the Human Cannabinoid Receptor Type 2 (CB2R) in the Brain with PET

Teodoro,

Gündel,

Deuther-Conrad

et al. 2023

J. Med. Chem.

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The development of cannabinoid receptor type 2 (CB2R) PET radioligands has been intensively explored due to the pronounced CB2R upregulation under various pathological conditions. Herein, we report on the synthesis of a series of CB2R affine fluorinated indole-2-carboxamide ligands. Compound RM365 was selected for PET radiotracer development due to its high CB2R affinity (K i = 2.1 nM) and selectivity over CB1R (factor > 300). Preliminary in vitro evaluation of [18F]RM365 indicated species differences in the binding to CB2R (K D of 2.32 nM for the hCB2R vs K D > 10,000 nM for the rCB2R). Metabolism studies in mice revealed a high in vivo stability of [18F]RM365. PET imaging in a rat model of local hCB2R(D80N) overexpression in the brain demonstrates the ability of [18F]RM365 to reach and selectively label the hCB2R(D80N) with a high signal-to-background ratio. Thus, [18F]RM365 is a very promising PET radioligand for the imaging of upregulated hCB2R expression under pathological conditions.

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“…The imaging of the CB2R in the brain with PET takes advantage of the very low level of expression of CB2R in healthy brain complemented by overexpression under pathological conditions, thus presumably resulting in a high signal-to-background ratio (SUVr). Up to date, none of the reported CB2R PET radioligands proved to be suitable for routine clinical use. − The development of radioligands for PET imaging of the CB2R in the brain is challenged by the generally inadequate pharmacological properties of the CB2R ligands (lipophilicity, metabolic stability, pharmacokinetic) and by the lack of a suitable animal model for the preclinical investigations. − …”

Section: Introductionmentioning

confidence: 99%

“…A number of 11 C and 18 F-labeled CB2R radioligands have been developed to date. − The most representative ones are shown in Figure . Early work by Evens and co-workers led to the development of [ 11 C]NE40 ( [ 11 C]1 ), , which was the only CB2R radioligand that was tested in human subjects .…”

Section: Introductionmentioning

confidence: 99%

Structure-Based Design, Optimization, and Development of [¹⁸F]LU13: A Novel Radioligand for Cannabinoid Receptor Type 2 Imaging in the Brain with PET

et al. 2022

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The cannabinoid receptor type 2 (CB2R) is an attractive target for the diagnosis and therapy of neurodegenerative diseases and cancer. In this study, we aimed at the development of a novel 18F-labeled radioligand starting from the structure of the known naphthyrid-2-one CB2R ligands. Compound 28 (LU13) was identified with the highest binding affinity and selectivity versus CB1R (CB2RK i = 0.6 nM; CB1RK i/CB2RK i > 1000) and was selected for radiolabeling with fluorine-18 and biological characterization. The new radioligand [ 18 F]LU13 showed high CB2R affinity in vitro as well as high metabolic stability in vivo. PET imaging with [ 18 F]LU13 in a rat model of vector-based/-related hCB2R overexpression in the striatum revealed a high signal-to-background ratio. Thus, [ 18 F]LU13 is a novel and highly promising PET radioligand for the imaging of upregulated CB2R expression under pathological conditions in the brain.

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PET Imaging of the Endocannabinoid System

Cited by 3 publications

References 472 publications

Development of [18F]LU14 for PET Imaging of Cannabinoid Receptor Type 2 in the Brain

Development of [18F]LU14 for PET Imaging of Cannabinoid Receptor Type 2 in the Brain

Synthesis, Structure–Activity Relationships, Radiofluorination, and Biological Evaluation of [¹⁸F]RM365, a Novel Radioligand for Imaging the Human Cannabinoid Receptor Type 2 (CB2R) in the Brain with PET

Structure-Based Design, Optimization, and Development of [¹⁸F]LU13: A Novel Radioligand for Cannabinoid Receptor Type 2 Imaging in the Brain with PET

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PET Imaging of the Endocannabinoid System

Cited by 3 publications

References 472 publications

Development of [18F]LU14 for PET Imaging of Cannabinoid Receptor Type 2 in the Brain

Development of [18F]LU14 for PET Imaging of Cannabinoid Receptor Type 2 in the Brain

Synthesis, Structure–Activity Relationships, Radiofluorination, and Biological Evaluation of [18F]RM365, a Novel Radioligand for Imaging the Human Cannabinoid Receptor Type 2 (CB2R) in the Brain with PET

Structure-Based Design, Optimization, and Development of [18F]LU13: A Novel Radioligand for Cannabinoid Receptor Type 2 Imaging in the Brain with PET

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Synthesis, Structure–Activity Relationships, Radiofluorination, and Biological Evaluation of [¹⁸F]RM365, a Novel Radioligand for Imaging the Human Cannabinoid Receptor Type 2 (CB2R) in the Brain with PET

Structure-Based Design, Optimization, and Development of [¹⁸F]LU13: A Novel Radioligand for Cannabinoid Receptor Type 2 Imaging in the Brain with PET