IMAGING OF DELTA-OPIOID RECEPTORS IN HUMAN BRAIN BY N1'-([C-11]METHYL)NALTRINDOLE AND PET

Recently, we have developed the positron emitting radiotracer N1'([C-1 1]methyl)naltrindole ([C-11]MeNTI) and demonstrated its high selectivi ty for delta opioid receptors in the mouse brain [Lever et al. (1992) fur. J. Pharmacol., 216:449-450]. In the present study, we examined th e selectivity of [C-11]MeNTI for the 6 opioid receptor in the human br ain, using positron emission tomography (PET). The regional kinetics a nd distribution as well as the pharmacology confirmed the selectivity of [C-11]MeNTI for delta opioid receptor in the human brain. First, th e regional kinetics of [C-11]MeNTI are in accordance with the density of the delta opioid receptor. Rapid washout in receptor-poor areas and prolonged retention in receptor-rich areas were observed. Second, the regional distribution of [C-11]MeNTI correlated well (r = 0.91) with the in vitro distribution of delta opioid sites but not with mu or kap pa site densities (r less than or equal to 0.008 or r less than or equ al to 0.014, respectively). [C-11]MeNTI binding was highest in regions of the neocortex (insular, parietal, frontal, cingulate, and occipita l), caudate nucleus, and putamen. Binding was intermediate in the amyg dala and lowest in the cerebellum and thalamus. Third, studies using t he competitive antagonist naltrexone demonstrated the inhibition of [C -11]MeNTI binding. Naltrexone inhibition of [C-11]MeNTI binding was mo st effective in delta receptor-rich regions, and its inhibitory potenc y correlated well (r = 0.88) with the regional distribution of delta o pioid sites. [C-11]MeNTI is the first radioligand which selectively la bels delta opioid receptors in vivo in the human brain following syste mic administration. The availability of [C-11]MeNTI will enable a rece ptor specific analysis of the role of [C-11]MeNTI receptors in normal and abnormal human brain. (C) 1996 Wiley-Liss, Inc.