Imaging of δ opioid receptors in human brain by N1'- ([¹¹C]methyl)naltrindole and PET

Recently, we have developed the positron emitting radiotracer N1'- ([¹¹C]methyl)naltrindole ([¹¹C]MeNTI) and demonstrated its high selectivity for δ opioid receptors in the mouse brain [Lever et al. (1992) Eur. J. Pharmacol., 216:449-450]. In the present study, we examined the selectivity of [¹¹C]MeNTI for the δ opioid receptor in the human brain, using positron emission tomography (PET). The regional kinetics and distribution as well as the pharmacology confirmed the selectivity of [¹¹C]MeNTI for δ opioid receptor in the human brain. First, the regional kinetics of [¹¹C]MeNTI are in accordance with the density of the δ opioid receptor. Rapid washout in receptor-poor areas and prolonged retention in receptor-rich areas were observed. Second, the regional distribution of [¹¹C]MeNTI correlated well (r = 0.91) with the in vitro distribution of opioid sites but not with μ or κ site densities (r ≤ 0.008 or r ≤ 0.014, respectively). [¹¹C]MeNTI binding was highest in regions of the neocortex (insular, parietal, frontal, cingulate, and occipital), caudate nucleus, and putamen. Binding was intermediate in the amygdala and lowest in the cerebellum and thalamus. Third, studies using the competitive antagonist naltrexone demonstrated the inhibition of [¹¹C]MeNTI binding. Naltrexone inhibition of [¹¹C]MeNTI binding was most effective in δ receptor-rich regions, and its inhibitory potency correlated well (r = 0.88) with the regional distribution of opioid sites. [¹¹C]MeNTI is the first radioligand which selectively labels δ opioid receptors in vive in the human brain following systemic administration. The availability of [¹¹C]MeNTI will enable a receptor specific analysis of the role of [¹¹C]MeNTI receptors in normal and abnormal human brain.