[123I]AM281 single-photon emission computed tomography imaging of central cannabinoid CB1 receptors before and after Δ9-tetrahydrocannabinol therapy and whole-body scanning for assessment of radiation dose in tourette patients

Berding, Georg; Müller‐Vahl, Kirsten; Schneider, Udo; Gielow, P.; Fitschen, Jürgen; Stuhrmann, Manfred; Harke, Heinrich; Buchert, Ralph; Donnerstag, Frank; Hofmann, Michael; Knoop, Bernd O.; Brooks, David J.; Emrich, H. M.; Knapp, Wolfram H.

doi:10.1016/j.biopsych.2004.01.005

Cited by 53 publications

(32 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the study of Wong et al [7], who found nonspecific changes in 5HT function in the brain of people with TS, Behen et al [25] used [ 11 C]methyl-L-tryptophan as nuclide to measure general Dopamine binding higher in basal ganglia Binding was not affected by symptoms Mena et al [18] 2004 TRODAT 1-Tc99m 10 Increased DAT bilaterally in striatum All patients treated with neuroleptics Hwang et al [19] 2008 TRODAT 1-Tc99m 10 No differences Yeh et al [20] 2007 TRODAT 1-Tc99m 8 Less decline in binding in striatum related to MPH challenge Bohnen et al [21] 1999 [ 11 C]Dihydrotetrabenazine 8 No difference Albin et al [22] 2003 [ 11 C]Dihydrotetrabenazine 19 Increased ventral striatal binding Berding et al [24] 2004 [ 123 I]AM281 6 Ligand detectable in people with TS Preliminary study 5HT function. They studied 29 children with TS and 9 healthy controls and focused their attention mainly on structures within the model of corticostriatothalamocortical (CSTC) circuitry.…”

Section: Studies Probing Particular Neurotransmitter Systemsmentioning

confidence: 99%

See 1 more Smart Citation

Functional neuroimaging in Tourette syndrome

Rickards¹

2009

Journal of Psychosomatic Research

View full text Add to dashboard Cite

Section: Studies Probing Particular Neurotransmitter Systemsmentioning

confidence: 99%

“…Berding et al [24] examined the cannabinoid CB1 ligand [ 123 I]AM281 in six TS patients before and after exposure to Δ 9 -tetrahydrocannabinol. They found that this ligand was detectable by SPECT in people with TS with an acceptably low exposure to radiation.…”

Section: Studies Probing Particular Neurotransmitter Systemsmentioning

confidence: 99%

Functional neuroimaging in Tourette syndrome

Rickards¹

2009

Journal of Psychosomatic Research

View full text Add to dashboard Cite

“…In vivo imaging of the CB1R using the novel PET tracer 18 F-MK-9470 (N-[2-(3-cyano-phenyl)-3-(4-(2-18 F-fluorethoxy)phenyl)-1-methylpropyl]-2-(5-methyl-2-pyridyloxy)-2-methylproponamide) is likely to expand our knowledge of various CNS pathophysiologic processes, neuropsychiatric disorders, and metabolic disorders, such as obesity, eating disorders, neurodegeneration, and epilepsy. Furthermore, this may provide a new diagnostic, prognostic, and monitoring biomarker that may enable prediction or evaluation of success or failure of related drug or interventional therapies, such as CB1R inverse agonist therapy for obesity or substance abuse (9)(10)(11). 18 F-MK-9470 (Merck Research Laboratories [MRL]) (12) is an inverse agonist with high selectivity and specificity for the human CB1R that allows preclinical and human imaging of the CB1R in the brain (13).…”

mentioning

confidence: 99%

Whole-Body Biodistribution and Radiation Dosimetry of the Human Cannabinoid Type-1 Receptor Ligand ¹⁸F-MK-9470 in Healthy Subjects

Laere¹,

Bohórquez²,

Goffin³

et al. 2008

J Nucl Med

View full text Add to dashboard Cite

The cannabinoid type-1 (CB1) receptor is one of the most abundant G-coupled protein receptors in the human body and is responsible for signal transduction of both endogenous and exogenous cannabinoids. The endocannabinoid system is strongly implicated in regulation of homeostasis and several neuropsychiatric disorders, obesity, and associated comorbidities, such as dyslipidemia and metabolic syndrome. We have used whole-body PET/CT to characterize the biodistribution and dosimetry of a novel high-affinity, subtype-selective radioligand, 18 F-MK-9470, in healthy male and female subjects. Methods: Eight nonobese subjects (5 men, 3 women; age, 22-54 y) underwent serial whole-body PET/CT for 6 h after a bolus injection of 251 6 25 MBq 18 F-MK-9470 (N-[2-(3-cyano-phenyl)-3-(4-(2-18 F-fluorethoxy)phenyl)-1-methylpropyl]-2-(5-methyl-2-pyridyloxy)-2-methylproponamide). Source organs were delineated 3-dimensionally using the combined morphologic and functional data. Residence times were derived from time-activity profiles using both the trapezoid rule and curve fitting. Individual organ doses and effective doses were determined using the OLINDA software package, with different approaches for gastrointestinal and urinary excretion modeling. Results: 18 F-MK-9470 is taken up slowly in the brain, reaching a plateau at approximately 90-120 min after bolus injection and is excreted predominantly through the hepatobiliary system. The gallbladder, upper large intestine, small intestine, and liver are the organs with the highest absorbed dose (average: 159, 98, 87, and 86 mGy/MBq, respectively). The mean effective dose (ED) was 22.8 6 4.3 mSv/MBq, indicating relatively low intersubject variability and a mean value in the range of many commercially available 18 F-labeled radiopharmaceuticals. Brain uptake was relatively high compared with that of existing central nervous system ligands for other receptors, between 3.2% and 4.9% of the injected dose. Conclusion: The estimated radiation burden of 18 F-MK-9470 for PET CB1 receptor imaging shows relatively low variability between subjects and has an acceptable ED, which allows multiple serial cerebral scans of good image quality, while remaining within the risk category class II-b defined by the World Health Organization and the International Commission for Radiation Protection for a standard injected activity (185-370 MBq).

show abstract

“…However, there is no evidence that TS is caused by mutations in the central cannabinoid receptor (CNR1) gene [48]. Studies using single photon emission tomography (SPET) and [ 123 I] AM281 to investigate central CB1 receptors have already been performed in humans, but are not yet suitable to clarify the functional role of CB1 receptors in TS [49].…”

Section: Central Cannabinoid Cb1 Receptor Systemmentioning

confidence: 99%

Cannabinoids reduce symptoms of Tourette’s syndrome

Müller‐Vahl

2003

Expert Opinion on Pharmacotherapy

View full text Add to dashboard Cite

Currently, the treatment of Tourette's syndrome (TS) is unsatisfactory. Therefore, there is expanding interest in new therapeutical strategies. Anecdotal reports suggested that the use of cannabis might improve not only tics, but also behavioural problems in patients with TS. A single-dose, cross-over study in 12 patients, as well as a 6-week, randomised trial in 24 patients, demonstrated that Delta9-tetrahydrocannabinol (THC), the most psychoactive ingredient of cannabis, reduces tics in TS patients. No serious adverse effects occurred and no impairment on neuropsychological performance was observed. If well-established drugs either fail to improve tics or cause significant adverse effects, in adult patients, therapy with Delta9-THC should be tried. At present, it remains unclear whether herbal cannabis, different natural or synthetic cannabinoid CB1-receptor agonists or agents that interfere with the inactivation of endocannabinoids, may have the best adverse effect profile in TS.

show abstract

[123I]AM281 single-photon emission computed tomography imaging of central cannabinoid CB1 receptors before and after Δ9-tetrahydrocannabinol therapy and whole-body scanning for assessment of radiation dose in tourette patients

Cited by 53 publications

References 46 publications

Functional neuroimaging in Tourette syndrome

Functional neuroimaging in Tourette syndrome

Whole-Body Biodistribution and Radiation Dosimetry of the Human Cannabinoid Type-1 Receptor Ligand ¹⁸F-MK-9470 in Healthy Subjects

Cannabinoids reduce symptoms of Tourette’s syndrome

Contact Info

Product

Resources

About

[123I]AM281 single-photon emission computed tomography imaging of central cannabinoid CB1 receptors before and after Δ9-tetrahydrocannabinol therapy and whole-body scanning for assessment of radiation dose in tourette patients

Cited by 53 publications

References 46 publications

Functional neuroimaging in Tourette syndrome

Functional neuroimaging in Tourette syndrome

Whole-Body Biodistribution and Radiation Dosimetry of the Human Cannabinoid Type-1 Receptor Ligand 18F-MK-9470 in Healthy Subjects

Cannabinoids reduce symptoms of Tourette’s syndrome

Contact Info

Product

Resources

About

Whole-Body Biodistribution and Radiation Dosimetry of the Human Cannabinoid Type-1 Receptor Ligand ¹⁸F-MK-9470 in Healthy Subjects