PT  - JOURNAL ARTICLE
AU  - Vijay, AIshwarya
AU  - Morris, Evan
AU  - Goldberg, Alissa
AU  - Petrulli, Joseph
AU  - Liu, Heather
AU  - Huang, Yiyun
AU  - Krishnan-Sarin, Suchitra
TI  - Naltrexone occupancy at kappa opioid receptors investigated in alcoholics by PET occupancy at kappa opioid receptors investigated in alcoholics by PET<strong/>
DP  - 2017 May 01
TA  - Journal of Nuclear Medicine
PG  - 1297--1297
VI  - 58
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/58/supplement_1/1297.short
4100  - http://jnm.snmjournals.org/content/58/supplement_1/1297.full
SO  - J Nucl Med2017 May 01; 58
AB  - 1297Objectives: 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.