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J Nucl Med. 2008; 49 (Supplement 1):234P
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Neurosciences: Psychiatry

Psychiatry Posters

Norepinephrine transporter imaging in cocaine abuse using (S,S)-[11C]MRB

Yu-Shin Ding1, Tarun Singhal1, Beata Planeta-Wilson1, Jean-Dominique Gallezot1, Shannan Henry1, Nabeel Nabulsi1, Jim Ropchan1, Richard Carson1, Alexander Neumeister1 and Robert Malison1

1 Yale University School of Medicine, New Haven, Connecticut

1008

Objectives: The role of the norepinephrine transporter (NET) in the reinforcing effects of stimulants, such as cocaine (COC), and the mechanisms responsible for their addictive and toxic effects has long been recognized; however, it has never been demonstrated via in vivo imaging due to lack of suitable NET radioligands. (S,S)-[11C]Methylreboxetine (MRB) is the most promising NET ligand. Here we report our preliminary studies to evaluate the role of NET in COC abuse.

Methods: Seventeen human volunteers (9 COC subjects and 8 healthy controls (HC)) underwent 120 min dynamic PET acquisition using HRRT after injection of 740 MBq of MRB. Parametric images were computed using the simplified reference tissue model (SRTM2; 2-parameter version) with occipital cortex as reference region. ROIs from the AAL template with additional small brain regions including locus coeruleus (LC), brainstem nuclei, hypothalamus (hypoTH), and thalamic subnuclei were analyzed. BPND (non-displaceable binding potential) values were compared between the two groups using unpaired t-test.

Results: An increase in BPND was observed for COC subjects as compared to HC for most NET rich regions (BPND≥0.5) such as in hypoTH, TH, and LC (36%, 21% and 50% [p=0.08], respectively). Among the thalamic subnuclei, the dorsomedial nucleus and pulvinar had a higher increase (36% and 43%) than ventrolateral nuclei (10%).

Conclusions: These data show a trend for altered NET in COC subjects with an upregulation in hypoTH, TH, and LC. This is the first report of altered NET regulation across brain regions in living human COC subjects. These results are consistent with upregulation in NET binding assessed by [3H]nisoxetine in monkeys after chronic cocaine exposure. More studies are needed to confirm these encouraging results.

Research Support: NIDA





This Article
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Right arrow Alert me to new issues of the journal
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Right arrow Articles by Malison, R.
PubMed
Right arrow Articles by Ding, Y.-S.
Right arrow Articles by Malison, R.