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Meeting ReportNeurosciences Track

Naltrexone occupancy at kappa opioid receptors investigated in alcoholics by PET occupancy at kappa opioid receptors investigated in alcoholics by PET

AIshwarya Vijay, Evan Morris, Alissa Goldberg, Joseph Petrulli, Heather Liu, Yiyun Huang and Suchitra Krishnan-Sarin
Journal of Nuclear Medicine May 2017, 58 (supplement 1) 1297;
AIshwarya Vijay
1Radiology and Biomedical Imaging Yale PET Center New Haven CT United States
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Evan Morris
4Radiology and Biomedical Imaging Yale University New Haven CT United States
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Alissa Goldberg
3Psychiatry Yale University New Haven CT United States
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Joseph Petrulli
2Biomedical Engineering Yale University New Haven CT United States
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Heather Liu
2Biomedical Engineering Yale University New Haven CT United States
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Yiyun Huang
4Radiology and Biomedical Imaging Yale University New Haven CT United States
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Suchitra Krishnan-Sarin
3Psychiatry Yale University New Haven CT United States
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Abstract

1297

Objectives: Earlier work from our group at Yale using a human alcohol drinking paradigm (ADP) suggested that family history (FH) of alcoholism and gender may mediate responses to Naltrexone (NTX) (1). NTX binds with varying degrees to Mu, Delta and Kappa opioid receptors and a further understanding of the association of clinical outcomes with receptor occupancy at each binding site could advance medication targeting for drinking behaviors. Weerts and colleagues (2) have shown negligible variability in percent occupancy of Mu receptors by NTX (95 +/- 5%) but high variability in occupany at Delta receptors (21 +/- 14%) in alcoholics using PET imaging. This suggests that action of NTX at Delta sites could explain variable outcomes of NTX treatment. The Kappa binding site was not interrogated at the time because there was no kappa tracer available. We have developed a selective Kappa PET tracer, 11C-LY2975050 (3). Our objective was to use PET imaging with 11C-LY2975050 to determine the level and the variability in NTX occupancy of Kappa receptors in alcoholics and to determine if occupancy and variability differs by sex and/or by FH of alcoholism.

Methods: Male and female alcoholics participated in the ADP as well as a baseline PET scan with 11C-LY2975050. Following 7 days of treatment with NTX (25mg, 50mg, 100mg remainder of week) they returned for a second ADP and a second PET scan.

Results: The mean NTX whole-brain occupancy at Kappa was 87.2 +/- 19.0% (n=33). There were no differences in mean occupancy between males (n=25) and females (n=8) 87.4 +/- 18.8% vs 86.4 +/- 22.1%, respectively. There were no differences in mean occupancy by family history (FHP: 88.1 +/- 16.2% (n=17) vs FHN: 86.2 +/- 22.6% (n=16)).

Conclusion: Our preliminary observations did not reveal differences in NTX binding to Kappa by sex or family history. It is interesting to note that we observed even greater variability in NTX binding to Kappa receptors than was observed at Delta, previously (2). Possible relationships between NTX binding at Kappa and changes in drinking behavior in the ADP sessions are being investigated. Research Support: NIH grant R01AA021818, JRP supported by NSF GRFP grant DGE-1122492 References: (1) Krishnan-Sarin S, Biological Psychiatry, 2007. (2) Weerts E, Neuropsychopharmacology, 2008. (3) Kim SJ, J Nuclear Medicine, 2013.

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Journal of Nuclear Medicine
Vol. 58, Issue supplement 1
May 1, 2017
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Naltrexone occupancy at kappa opioid receptors investigated in alcoholics by PET occupancy at kappa opioid receptors investigated in alcoholics by PET
AIshwarya Vijay, Evan Morris, Alissa Goldberg, Joseph Petrulli, Heather Liu, Yiyun Huang, Suchitra Krishnan-Sarin
Journal of Nuclear Medicine May 2017, 58 (supplement 1) 1297;

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Naltrexone occupancy at kappa opioid receptors investigated in alcoholics by PET occupancy at kappa opioid receptors investigated in alcoholics by PET
AIshwarya Vijay, Evan Morris, Alissa Goldberg, Joseph Petrulli, Heather Liu, Yiyun Huang, Suchitra Krishnan-Sarin
Journal of Nuclear Medicine May 2017, 58 (supplement 1) 1297;
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