PT  - JOURNAL ARTICLE
AU  - Wong, Dean
AU  - Kuwabara, Hiroto
AU  - Horti, Andrew
AU  - Kumar, Anil
AU  - Brasic, James
AU  - Ye, Weiguo
AU  - Alexander, Mohab
AU  - Hilton, John
AU  - Williams, V.
AU  - Roberson, M.
AU  - Ravert, Hayden
AU  - Dannals, Robert
TI  - Imaging of human cannabinoid CB1 receptors with [11C]OMAR
DP  - 2008 May 01
TA  - Journal of Nuclear Medicine
PG  - 131P--131P
VI  - 49
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/49/supplement_1/131P.4.short
4100  - http://jnm.snmjournals.org/content/49/supplement_1/131P.4.full
SO  - J Nucl Med2008 May 01; 49
AB  - 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.