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J Nucl Med. 2008; 49 (Supplement 1):131P
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Neurosciences: Psychiatry

Neurotransmission - Beyond Dopamine

Imaging of human cannabinoid CB1 receptors with [11C]OMAR

Dean Wong1, Hiroto Kuwabara1, Andrew Horti1, Anil Kumar1, James Brasic1, Weiguo Ye1, Mohab Alexander1, John Hilton1, V. Williams1, M. Roberson1, Hayden Ravert1 and Robert Dannals1

1 Radiology, Johns Hopkins Medical Institutions, Baltimore, Maryland

523

Objectives: The cannabinoid CB1 receptor is of great interest for disorders of Neuropsychiatry and as a therapeutic target. We present the 1st human studies with [11C]OMAR a.k.a. [11C]JHU75528, previously shown to have specific binding and receptor distribution to CB1 in mice and baboons (Horti, 2006).

Methods: Dynamic 90 min PET scans on the Hi Resolution (HRRT) were done ,with a mean specific activity of 310 GBq/micromol and injected mass of 1.1 ± 0.2 mcg and activity 19.2 ± 1 mCi (710 MBq) in 7 normal volunteers, mean of 28.6 ± 7 yrs, all male. Each had SPGR MRI and arterial sampling with HPLC metabolites. Modeling consisted of a total distribution volume (VT) estimated in each brain region using Logan plasma reference and 2 tissue comp with constraint with 5 parameters(TTCM-5C).

Results: The mean remaining parent tracer was 41% at 60 min. The radiotracer showed good brain uptake with peak % SUV 136 to 207% ~20 min in putamen. Radioactivity decreased gradually thereafter and reached % SUV from 80 to 117% in putamen, which confirmed reversibility. The mean volume (VT) ranged from 1-1.7 in multiple cortical and subcortical regions and showed PET regional distribution that correlated well with postmortem distribution of CB1 and with highest binding in CB1 rich-regions (Cingulate, Globus pallidus, Putamen) Logan plots showed excellent linearity (R2>0.93) using frames obtained between 30 and 90 min and excellent agreement with TTCM-5C (R2=0.98).

Conclusions: These human PET studies suggest that [11C]OMAR has good quantification characteristics suitable for further disease and drug development applications. It is superior to [18F]MK9470 that displayed very slow brain kinetics and at least comparable to other recently published CB1 PET radioligands studied in non-human primates.





This Article
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Right arrow Articles by Wong, D.
Right arrow Articles by Dannals, R.
PubMed
Right arrow Articles by Wong, D.
Right arrow Articles by Dannals, R.