ORIGINAL ARTICLE Biodistribution and radiation dosimetry of the norepinephrine transporter radioligand (S,S)-[ 18 F]FMeNER-D 2 : a human whole-body PET study Akihiro Takano & Christer Halldin & Andrea Varrone & Per Karlsson & Nils Sjöholm & James B. Stubbs & Magnus Schou & Anu J. Airaksinen & Johannes Tauscher & Balázs Gulyás Received: 5 March 2007 / Accepted: 28 September 2007 / Published online: 14 November 2007 # Springer-Verlag 2007 Abstract Purpose (S,S)-[ 18 F]FMeNER-D 2 is a recently developed positron-emission tomography (PET) radioligand for in vivo quantification of the norepinephrine transporter system. The aim of this study was to provide dosimetry estimates for (S,S)-[ 18 F]FMeNER-D 2 based on human whole-body PET measurements. Methods PET scans were performed for a total of 6.4 h after the injection of 168.9 ± 31.5 MBq of (S,S)-[ 18 F]FMeNER-D 2 in four healthy male subjects. Volumes of interest were drawn on the coronal images. Estimates of the absorbed dose of radiation were calculated using the OLINDA software. Results Uptake was largest in lungs, followed by liver, bladder, brain and other organs. Peak values of the percent injected dose (%ID) at a time after radioligand injection were calculated for the lung (21.6%ID at 0.3 h), liver (5.1%ID at 0.3 h), bladder (12.2%ID at 6 h) and brain (2.3%ID at 0.3 h). The largest absorbed dose was found in the urinary bladder wall (0.039 mGy/MBq). The calculated effective dose was 0.017 mSv/MBq. Conclusion Based on the distribution and dose estimates, the estimated radiation burden of (S,S)-[ 18 F]FMeNER-D 2 is lower than that of [ 18 F]FDG. The radioligand would allow multiple PET examinations in the same research subject per year. Keywords Dosimetry . Norepinephrine transporter . (S,S)-[ 18 F]FMeNER-D 2 Introduction The neurotransmitter norepinephrine plays an important role in the regulation of various brain functions, such as affective states, learning and memory, endocrine and autonomic functions. The norepinephrine transporter (NET) is respon- sible for the reuptake of norepinephrine into the presynaptic nerve terminals [1, 2]. NET plays an important physiolog- ical role in the regulation of norepinephrine transmission. Abnormalities in brain NET have been supposed to be associated with a variety of neuropsychiatric diseases such as mood disorder and attention deficit hyperactivity disorder (ADHD) [3, 4]. A NE reuptake inhibitor reboxetine has been observed to be as effective as imipramine and fluoxetine in the treatment of depression [5, 6]. Recently, atomoxetine, a selective norepinephrine reuptake inhibitor (K i value 5 nM), has been found to be effective for the treatment of ADHD [7–9]. For these reasons, the in vivo imaging of the regional distribution of NET in the human brain has become a research topic of high importance and priority. The measurement of regional NET levels in the living human brain has been hampered by the lack of suitable positron-emission tomography (PET) radioligands for NET. Eur J Nucl Med Mol Imaging (2008) 35:630–636 DOI 10.1007/s00259-007-0622-z A. Takano : C. Halldin : A. Varrone : P. Karlsson : N. Sjöholm : M. Schou : A. J. Airaksinen : B. Gulyás (*) Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm 171 76, Sweden e-mail: Balazs.Gulyas@ki.se J. B. Stubbs Radiation Dosimetry Systems, Inc, Palo Alto, CA, USA J. Tauscher Lilly Research Laboratories, Indianapolis, IN, USA