11C-JHU75528: A radiotracer for PET imaging of CB1 cannabinoid receptors

Andrew Horti, Hong Fan, Hiroto Kuwabara, John Hilton, Hayden T. Ravert, Daniel Holt, Mohab Alexander, Anil Kumar, Arman Rahmim, Ursula Scheffel, Dean Foster Wong, Robert F Dannals

Research output: Contribution to journalArticle

Abstract

The development of the radioligands for PET imaging of the cerebral cannabinoid receptor (CB1) is of great importance for studying its role in neuropsychiatric disorders, obesity, and drug dependence. None of the currently available radioligands for CB1 are suitable for quantitative PET, primarily because of their insufficient binding potential (BP) in brain or low penetration through the blood-brain barrier (BBB). The goal of this study was to evaluate 11C-JHU75528, an analog of the selective CB1 antagonist rimonabant, in vivo as a potential CB1 radioligand for PET. Methods: The brain regional distribution and pharmacology of 11C-JHU75528 have been evaluated in vivo in mice (dissection) and baboons (PET). Results: 11C-JHU75528 readily entered the mouse and baboon brain and specifically and selectively labeled cerebral CB1 receptors. The ratio of striatum to brain stem in mice and the binding potential (BP) in the baboon putamen were 3.4 and 1.321.5, respectively. The specific binding of 11C-JHU75528 in vivo was blocked by preinjection of nonlabeled JHU75528. Administration of rimonabant (1 mg/kg, intravenously) also blocked the specific binding of 11C- JHU75528 in the mouse and baboon brain, whereas various central non-cannabinoid drugs did not significantly reduce the 11C-JHU75528 binding in the mouse brain. 11C-JHU75528 formed several hydrophilic metabolites, but only a minute fraction of metabolic radioactivity penetrated the BBB. Conclusion: 11C-JHU75528 holds promise as a radiotracer with suitable imaging properties for quantification of CB1 receptors in the human brain.

Original languageEnglish (US)
Pages (from-to)1689-1696
Number of pages8
JournalJournal of Nuclear Medicine
Volume47
Issue number10
StatePublished - Oct 1 2006

Fingerprint

Cannabinoid Receptor CB1
rimonabant
Papio
Brain
Blood-Brain Barrier
4-cyano-1-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide
Putamen
Radioactivity
Brain Stem
Substance-Related Disorders
Dissection
Obesity
Pharmacology

Keywords

  • C-JHU75528
  • Cannabinoid receptor
  • PET

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

11C-JHU75528 : A radiotracer for PET imaging of CB1 cannabinoid receptors. / Horti, Andrew; Fan, Hong; Kuwabara, Hiroto; Hilton, John; Ravert, Hayden T.; Holt, Daniel; Alexander, Mohab; Kumar, Anil; Rahmim, Arman; Scheffel, Ursula; Wong, Dean Foster; Dannals, Robert F.

In: Journal of Nuclear Medicine, Vol. 47, No. 10, 01.10.2006, p. 1689-1696.

Research output: Contribution to journalArticle

Horti, A, Fan, H, Kuwabara, H, Hilton, J, Ravert, HT, Holt, D, Alexander, M, Kumar, A, Rahmim, A, Scheffel, U, Wong, DF & Dannals, RF 2006, '11C-JHU75528: A radiotracer for PET imaging of CB1 cannabinoid receptors', Journal of Nuclear Medicine, vol. 47, no. 10, pp. 1689-1696.
Horti, Andrew ; Fan, Hong ; Kuwabara, Hiroto ; Hilton, John ; Ravert, Hayden T. ; Holt, Daniel ; Alexander, Mohab ; Kumar, Anil ; Rahmim, Arman ; Scheffel, Ursula ; Wong, Dean Foster ; Dannals, Robert F. / 11C-JHU75528 : A radiotracer for PET imaging of CB1 cannabinoid receptors. In: Journal of Nuclear Medicine. 2006 ; Vol. 47, No. 10. pp. 1689-1696.
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abstract = "The development of the radioligands for PET imaging of the cerebral cannabinoid receptor (CB1) is of great importance for studying its role in neuropsychiatric disorders, obesity, and drug dependence. None of the currently available radioligands for CB1 are suitable for quantitative PET, primarily because of their insufficient binding potential (BP) in brain or low penetration through the blood-brain barrier (BBB). The goal of this study was to evaluate 11C-JHU75528, an analog of the selective CB1 antagonist rimonabant, in vivo as a potential CB1 radioligand for PET. Methods: The brain regional distribution and pharmacology of 11C-JHU75528 have been evaluated in vivo in mice (dissection) and baboons (PET). Results: 11C-JHU75528 readily entered the mouse and baboon brain and specifically and selectively labeled cerebral CB1 receptors. The ratio of striatum to brain stem in mice and the binding potential (BP) in the baboon putamen were 3.4 and 1.321.5, respectively. The specific binding of 11C-JHU75528 in vivo was blocked by preinjection of nonlabeled JHU75528. Administration of rimonabant (1 mg/kg, intravenously) also blocked the specific binding of 11C- JHU75528 in the mouse and baboon brain, whereas various central non-cannabinoid drugs did not significantly reduce the 11C-JHU75528 binding in the mouse brain. 11C-JHU75528 formed several hydrophilic metabolites, but only a minute fraction of metabolic radioactivity penetrated the BBB. Conclusion: 11C-JHU75528 holds promise as a radiotracer with suitable imaging properties for quantification of CB1 receptors in the human brain.",
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AU - Kumar, Anil

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