Literature DB >> 20333514

Biodistribution and dosimetry in humans of two inverse agonists to image cannabinoid CB1 receptors using positron emission tomography.

Garth E Terry1, Jussi Hirvonen, Jeih-San Liow, Nicholas Seneca, Johannes T Tauscher, John M Schaus, Lee Phebus, Christian C Felder, Cheryl L Morse, Victor W Pike, Christer Halldin, Robert B Innis.   

Abstract

PURPOSE: Cannabinoid subtype 1 (CB(1)) receptors are found in nearly every organ in the body, may be involved in several neuropsychiatric and metabolic disorders, and are therefore an active target for pharmacotherapy and biomarker development. We recently reported brain imaging of CB(1) receptors with two PET radioligands: (11)C-MePPEP and (18)F-FMPEP-d (2). Here we describe the biodistribution and dosimetry estimates for these two radioligands.
METHODS: Seven healthy subjects (four men and three women) underwent whole-body PET scans for 120 min after injection with (11)C-MePPEP. Another seven healthy subjects (two men and five women) underwent whole-body PET scans for 300 min after injection with (18)F-FMPEP-d (2). Residence times were acquired from regions of interest drawn on tomographic images of visually identifiable organs for both radioligands and from radioactivity excreted in urine for (18)F-FMPEP-d (2).
RESULTS: The effective doses of (11)C-MePPEP and (18)F-FMPEP-d (2) are 4.6 and 19.7 microSv/MBq, respectively. Both radioligands demonstrated high uptake of radioactivity in liver, lung, and brain shortly after injection and accumulated radioactivity in bone marrow towards the end of the scan. After injection of (11)C-MePPEP, radioactivity apparently underwent hepatobiliary excretion only, while radioactivity from (18)F-FMPEP-d (2) showed both hepatobiliary and urinary excretion.
CONCLUSION: (11)C-MePPEP and (18)F-FMPEP-d (2) yield an effective dose similar to other PET radioligands labeled with either (11)C or (18)F. The high uptake in brain confirms the utility of these two radioligands to image CB(1) receptors in brain, and both may also be useful to image CB(1) receptors in the periphery.

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Year:  2010        PMID: 20333514      PMCID: PMC2916034          DOI: 10.1007/s00259-010-1411-7

Source DB:  PubMed          Journal:  Eur J Nucl Med Mol Imaging        ISSN: 1619-7070            Impact factor:   9.236


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