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

Madar, Igal; Lever, John R.; Kinter, Chris M.; Scheffel, Ursula; Ravert, Hayden T.; Musachio, John L.; Mathews, William B.; Dannals, Robert F.; Frost, J. James

doi:10.1002/(sici)1098-2396(199609)24:1<19::aid-syn3>3.0.co;2-j

Cited by 78 publications

(61 citation statements)

References 27 publications

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“…In the current study, d-OR K i at baseline was highest in neocortical regions (insular, parietal, frontal, cingulate, and occipital), caudate nucleus, and putamen, and lowest in the cerebellum and thalamus. The brain regions of high binding determined with Patlak slope in the current study are consistent with those determined in our previous studies (Madar et al, 1996) in which [ 11 C]MeNTI normalized binding to d-OR receptors was calculated using the cerebellum as a reference region (ROI minus cerebellum/ cerebellum). Patlak graphical analysis was selected for use in the current study based on our findings in our previous study (Smith et al, 1999) that evaluated both kinetic (twoand three-compartment models, Patlak graphical analysis) and nonkinetic (apparent volume of distribution and activity at a late scanning time) analytic approaches.…”

Section: Discussionmentioning

confidence: 99%

“…11 C]MeNTI shows irreversible binding characteristics during the 90-min scan period (Madar et al, 1996). In the current study, treatment with 50 mg naltrexone resulted in a partial (mean: 21%) inhibition of d-OR K i across ROIs when compared with the pre-naltrexone baseline.…”

Section: Discussionmentioning

confidence: 99%

“…11 C]MeNTI, a specific d-OR agonist, developed for PET imaging (Lever et al, 1992;Madar et al, 1996). On each day, PET imaging was conducted; there was a fixed order for the two scans; the [ 11 C]MeNTI scan was initiated at 0830 followed by the [ 11 C]CAR scan at 1045.…”

Section: Race (N)mentioning

confidence: 99%

“…We selected this approach because our previous study demonstrated that dissociation of the ligand was not evident for 90 min post injection (Madar et al, 1996;Smith et al, 1999).…”

Section: Pet Image Analysismentioning

confidence: 99%

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Differences in δ- and μ-Opioid Receptor Blockade Measured by Positron Emission Tomography in Naltrexone-Treated Recently Abstinent Alcohol-Dependent Subjects

Weerts

Kim

Wand

et al. 2007

Neuropsychopharmacol

138

147

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Blockade of brain m-opioid receptor (m-OR) and d-opioid receptor (d-OR) was investigated in recently abstinent alcohol-dependent subjects (N ¼ 21) maintained on naltrexone. Subjects completed a 19-day inpatient protocol, which included alcohol abstinence followed by naltrexone treatment (50 mg) on days 15-19. Blood samples were collected after the first administration of naltrexone to evaluate serum levels of naltrexone and 6-b-naltrexol. Regional brain m-OR binding potential (BP) and d-OR K i was measured using [ 11 C]carfentanil (CAR) positron emission tomography (PET) and [11 C]methyl naltrindole ([ 11 C]MeNTI) PET, respectively, before (day 5) and during naltrexone treatment (day 18). Naltrexone inhibition of [ 11 C]CAR BP was near maximal across all brain regions of interest with little variability across subjects (mean + SD% inhibition ¼ 94.9 + 4.9%). Naltrexone only partially inhibited the [ 11 C]MeNTI K i and there was more variability across subjects (mean + SD% inhibition ¼ 21.1 + 14.49%). Peak serum levels of naltrexone were positively correlated with % inhibition of d-OR K i in neocortex and basal ganglia. Peak serum levels of naltrexone were not correlated with % inhibition of m-OR BP. Peak levels of 6-b-naltrexol were not significantly correlated with % inhibition of m-OR BP or d-OR K i . Thus, the FDA recommended therapeutic dose of naltrexone was sufficient to produce near complete inhibition of the m-OR in recently abstinent alcohol dependent subjects. The lower percent inhibition of d-OR and greater variability in d-OR blockade by naltrexone across subjects may contribute to individual differences in treatment outcomes to naltrexone. Further investigations on the relationship between individual differences in d-OR blockade by naltrexone and clinical outcomes should be explored.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Race (N)mentioning

confidence: 99%

“…We selected this approach because our previous study demonstrated that dissociation of the ligand was not evident for 90 min post injection (Madar et al, 1996;Smith et al, 1999).…”

Section: Pet Image Analysismentioning

confidence: 99%

See 2 more Smart Citations

Differences in δ- and μ-Opioid Receptor Blockade Measured by Positron Emission Tomography in Naltrexone-Treated Recently Abstinent Alcohol-Dependent Subjects

Weerts

Kim

Wand

et al. 2007

Neuropsychopharmacol

138

147

View full text Add to dashboard Cite

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“…[ 11 C]carfentanil ([ 11 C]CFN) and [ 11 C]-N-methyl-naltrindole ([ 11 C]MeNTl) are highly selective radioligands for µ and δ opioid receptors respectively and have been used to image central opioid receptors with PET [12,13]. The goal of this preliminary study was to assess the feasibility of imaging µ and δ opioid receptors in the human myocardium with [ 11 C]CFN and [ 11 C]MeNTI in vivo with PET.…”

Section: Introductionmentioning

confidence: 99%

PET imaging of human cardiac opioid receptors

et al. 2002

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The presence of opioid peptides and receptors and their role in the regulation of cardiovascular function has been previously demonstrated in the mammalian heart. The aim of this study was to image micro and delta opioid receptors in the human heart using positron emission tomography (PET). Five subjects (three females, two males, 65+/-8 years old) underwent PET scanning of the chest with [(11)C]carfentanil ([(11)C]CFN) and [(11)C]- N-methyl-naltrindole ([(11)C]MeNTI) and the images were analyzed for evidence of opioid receptor binding in the heart. Either [(11)C]CFN or [(11)C]MeNTI (20 mCi) was injected i.v. with subsequent dynamic acquisitions over 90 min. For the blocking studies, either 0.2 mg/kg or 1 mg/kg of naloxone was injected i.v. 5 min prior to the injection of [(11)C]CFN and [(11)C]MeNTI, respectively. Regions of interest were placed over the left ventricle, left ventricular chamber, lung and skeletal muscle. Graphical analysis demonstrated average baseline myocardial binding potentials (BP) of 4.37+/-0.91 with [(11)C]CFN and 3.86+/-0.60 with [(11)C]MeNTI. Administration of 0.2 mg/kg naloxone prior to [(11)C]CFN produced a 25% reduction in BP in one subject in comparison with baseline values, and a 19% decrease in myocardial distribution volume (DV). Administration of 1 mg/kg of naloxone before [(11)C]MeNTI in another subject produced a 14% decrease in BP and a 21% decrease in the myocardial DV. These results demonstrate the ability to image these receptors in vivo by PET. PET imaging of cardiac opioid receptors may help to better understand their role in cardiovascular pathophysiology and the effect of abuse of opioids and drugs on heart function.

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Autoradiographic and SPECT imaging of cerebral opioid receptors with an iodine-123 labeled analogue of diprenorphine

Lever

Ilgìn

Musachio

et al. 1998

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The feasibility of imaging cerebral opioid receptors by single photon emission computed tomography (SPECT) has been established in baboon using a novel analog of diprenorphine (DPN) radiolabeled with iodine-123. The radioligand, [123I]-O-IA-DPN (C6-O-[123I]iodoallyl-DPN), was prepared in good yield (80%) with high radiochemical purity (>97%) and high specific radioactivity (>2,400 mCi/micromol). In ex vivo autoradiographic studies, with and without naltrexone blockade, [123I]-O-IA-DPN specifically labeled opioid receptors throughout the mouse brain. Nonmetabolized radioligand accounted for >90% of the signal observed in extracts of whole mouse brain. SPECT imaging trials showed that [123I]-O-IA-DPN selectively localized in regions of baboon brain known to have high densities of opioid receptors, such as striatum, thalamus, and temporal cortex. A much lower level of radioligand uptake and retention was noted for cerebellum, a region with few opioid binding sites. Pretreatment with naltrexone (6.5 pmol/kg) blocked [123I]-O-IA-DPN binding in all brain regions. Using naltrexone blockade to define the nonspecific component for a given region of interest, total to nonspecific binding ratios increased linearly (r > or = 0.98) over the SPECT study with maximal values for striatum (9.8), thalamus (7.1), and temporal cortex (6.9) reached at the last time point investigated (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 of the time course, specific [123I]-O-IA-DPN binding was >85% of total radioactivity in regions rich in opioid receptors and 62% of total radioactivity in cerebellum. The aggregate data are consistent with visualization of multiple opioid receptor types. Thus, [123I]-O-IA-DPN should prove useful for SPECT studies within the constraints imposed by a lack of innate selectivity for a single type of brain opioid receptor.

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

Cited by 78 publications

References 27 publications

Differences in δ- and μ-Opioid Receptor Blockade Measured by Positron Emission Tomography in Naltrexone-Treated Recently Abstinent Alcohol-Dependent Subjects

Differences in δ- and μ-Opioid Receptor Blockade Measured by Positron Emission Tomography in Naltrexone-Treated Recently Abstinent Alcohol-Dependent Subjects

PET imaging of human cardiac opioid receptors

Autoradiographic and SPECT imaging of cerebral opioid receptors with an iodine-123 labeled analogue of diprenorphine

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