RT Journal Article
SR Electronic
T1 PET imaging of norepinephrine transporter in adults with attention deficit hyperactivity disorder
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 330
OP 330
VO 51
IS supplement 2
A1 Ding, Yu-Shin
A1 Planeta-Wilson, Beata
A1 Gallezot, Jean-Dominique
A1 Lin, Shu-fei
A1 Williams, Wendol
A1 Carson, Richard
A1 Van Dyck, Christopher
YR 2010
UL http://jnm.snmjournals.org/content/51/supplement_2/330.abstract
AB 330 Objectives We have previously shown that methylphenidate, the most commonly used drug for treatment of attention deficit hyperactivity disorder (ADHD), significantly occupies the norepinephrine transporter (NET) at clinically relevant doses with an ED50 even more potent than that for the dopamine transporter (i.e., an ED50 value of 0.14 and 0.25 mg/kg for NET and DAT, respectively), suggesting an important role for NET in ADHD. The purpose of this study is to determine whether adults with ADHD have altered NET availability compared to matched controls (HC) as measured by the ligand (S,S)-[11C]MRB ([11C]MRB) and PET. Methods Human volunteers (ADHD: n=3 and HC: n=11) underwent dynamic PET acquisition using HRRT for 120 min following a bolus injection of ~740 MBq of [11C]MRB. Binding potential (BPND) images were computed using the multilinear reference tissue model (2-parameter version: MRTM2 with t*=20) with occipital cortex as the reference region. The mean BPND values were estimated for 11 ROIs (including small brain regions; i.e., locus coeruleus (LC), brainstem nuclei, hypothalamus (hypoTH), and thalamic subnuclei) and compared between the two groups using two-tailed unpaired t-test. Results The BPND values from ADHD adults, who meet DSM-IV criteria and have not used stimulants for at least 4 years before the study, were compared with the mean BPND values obtained from HCs. Decreased regional BPND values in ADHD subjects were observed in most NET-rich regions; e.g., LC (~17% decrease), hypoTH (31-55% decrease), nucleus ruber (49%, p=0.04), thalamus (25%, p=0.01) and thalamic subnuclei: dorsomedial (22-38%, p=0.04) and pulvinar (26-44%). Conclusions These preliminary data show a trend for altered NET in ADHD subjects, with a downregulation in most NET-rich regions. More ADHD subjects are under investigation to confirm these encouraging results. Research Support NIH/NID