AUTORADIOGRAPHIC AND SPECT IMAGING OF CEREBRAL OPIOID RECEPTORS WITH AN I-123 LABELED ANALOG OF DIPRENORPHINE

The feasibility of imaging cerebral opioid receptors by single photon emission computed tomography (SPECT) has been established in baboon us ing a novel analog of diprenorphine (DPN) radiolabeled with iodine-123 . The radioligand, [I-123]-O-IA-DPN (C6-O-[I-123]iodoallyl-DPN), was p repared in good yield (80%) with high radiochemical purity (>97%) and high specific radioactivity (>2,400 mCi/mu mol). In ex vivo autoradiog raphic studies, with and without naltrexone blockade, [I-I23]-O-IA-DPN specifically labeled opioid receptors throughout the mouse brain. Non metabolized radioligand accounted for >90% of the signal observed in e xtracts of whole mouse brain. SPECT imaging trials showed that [I-123] -O-IA-DPN selectively localized in regions of baboon brain known to ha ve high densities of opioid receptors, such as striatum, thalamus, and temporal cortex. A much lower level of radioligand uptake and retenti on was noted for cerebellum, a region with few opioid binding sites. P retreatment with naltrexone (6.5 mu mol/kg) blocked [I-I23]-O-IA-DPN b inding in all brain regions. Using naltrexone blockade to define the n onspecific component for a given region of interest, total to nonspeci fic binding ratios increased linearly (r greater than or equal to 0.98 ) over the SPECT study with maximal values for striatum (9.8), thalamu s (7.1), and temporal cortex (6.9) reached at the last time point inve stigated (3.5 h). Specific binding for these regions, assessed as the difference between regional SPECT activity for the control and blocked states, proved irreversible over the observation period. By the end o f the time course, specific [I-123]-O-IA-DPN binding was >85% of total radioactivity in regions rich in opioid receptors and 62% of total ra dioactivity in cerebellum. The aggregate data are consistent with visu alization of multiple opioid receptor types. Thus, [I-123]-O-IA-DPN sh ould prove useful for SPECT studies within the constraints imposed by a lack of innate selectivity for a single type of brain opioid recepto r. (C) 1998 Wiley-Liss, Inc.