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3,5-bis(Trifluoromethyl)pyrazolines as Non-Invasive PET Radioligands for CB(1) Receptor Imaging in Live Mice.
The cannabinoid receptor 1 (CB(1)) is an attractive target for non-invasive imaging of CB(1) receptor-expressing brain structures in the living brain using positron emission tomography (PET). Thus far, most of the PET tracers that were developed for CB(1) imaging have been fluorinated analogs of the classical cannabinoid agonist 2-methyl-6-(3-hydroxypropyl)phenanthrene (WIN55,212-2). Although these analogs allow precise determination of CB(1) receptor occupancy in the living brain, these radioligands also bind to peripheral CB(1) receptors that are likely involved in central actions other than those mediated via CB(1) receptors. Thus, it would be advantageous to have a PET tracer that is selective for CB(1) receptors. Here we describe a new class of non-selective PET tracers, 3,5-bis(trifluoromethyl)pyrazolines, that bind selectively to the CB(1) receptor with high affinity and selectivity over all other receptors that have been cloned or cloned to date. Thus, these PET tracers do not cross the blood-brain barrier and, therefore, are not suitable for in vivo studies of CB(1) receptor distribution in the living brain. However, we show that 3,5-bis(trifluoromethyl)pyrazolines can be used for in vivo visualization of peripheral CB(1) receptors using microPET. Thus, these new PET tracers will serve as useful tools for elucidating the role of peripheral CB(1) receptors in physiological and pathological processes.Q:
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