Abstract
Purpose
(S,S)-[18F]FMeNER-D2 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)-[18F]FMeNER-D2 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)-[18F]FMeNER-D2 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)-[18F]FMeNER-D2 is lower than that of [18F]FDG. The radioligand would allow multiple PET examinations in the same research subject per year.
Similar content being viewed by others
References
Blakely RD, De Felice LJ, Hartzell HC. Molecular physiology of norepinephrine and serotonin transporters. J Exp Biol 1994;196:263–81.
Galli A, DeFelice LJ, Duke BJ, Moore KR, Blakely RD. Sodium-dependent norepinephrine-induced currents in norepinephrine-transporter-transfected HEK-293 cells blocked by cocaine and antidepressants. J Exp Biol 1995;198:2197–212.
Biederman J, Spencer T. Attention-deficit/hyperactivity disorder (ADHD) as a norepinephrine disorder. Biol Psychiatry 1999;46:1234–42.
Roy A, Pickar D, De Jong J, Karoum F, Linnoila M. Norepinephrine and its metabolites in cerebrospinal fluid, plasma, and urine. Relationship to hypothalamic-pituitary-adrenal axis function in depression. Arch Gen Psychiatry 1988;45:849–57.
Berzewski H, Van Moffaert M, Gagiano CA. Efficacy and tolerability of reboxetine compared with imipramine in a double-blind study in patients suffering from major depressive offsodes. Eur Neuropsychopharmacol 1997;7(Suppl 1):S37–47.
Massana J. Reboxetine versus fluoxetine: an overview of efficacy and tolerability. J Clin Psychiatry 1998;59(Suppl 14):8–10.
Spencer T, Biederman J, Wilens T, Prince J, Hatch M, Jones J, et al. Effectiveness and tolerability of tomoxetine in adults with attention deficit hyperactivity disorder. Am J Psychiatry 1998;155:693–5.
Michelson D, Faries D, Wernicke J, Kelsey D, Kendrick K, Sallee FR, et al. Atomoxetine ADHD Study Group. Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, dose-response study. Pediatrics 2001;108:E83.
Bymaster FP, Katner JS, Nelson DL, Hemrick-Luecke SK, Threlkeld PG, Heiligenstein JH, et al. Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology 2002;27:699–711.
Schou M, Halldin C, Sovago J, Pike VW, Gulyas B, Mozley PD, et al. Specific in vivo binding to the norepinephrine transporter demonstrated with the PET radioligand, (S,S)-[11C]MeNER. Nucl Med Biol 2003;30:707–14.
Schou M, Halldin C, Sovago J, Pike VW, Hall H, Gulyas B, et al. PET evaluation of novel radiofluorinated reboxetine analogs as norepinephrine transporter probes in the monkey brain. Synapse 2004;53:57–67.
Seneca N, Gulyas B, Varrone A, Schou M, Airaksinen A, Tauscher J, et al. Atomoxetine occupies the norepinephrine transporter in a dose-dependent fashion: a PET study in nonhuman primate brain using (S,S)-[18F]FMeNER-D2.Psychopharmacology (Berl) 2006;188:119–27.
Seneca N, Andree B, Sjoholm N, Schou M, Pauli S, Mozley PD, et al. Whole-body biodistribution, radiation dosimetry estimates for the PET norepinephrine transporter probe (S,S)-[18F]FMeNER-D2 in non-human primates. Nucl Med Commun 2005;26:695–700.
Wrobel MC, Carey JE, Sherman PS, Kilbourn MR. Simplifying the dosimetry of carbon-11-labeled radiopharmaceuticals. J Nucl Med 1997;38:654–60.
Cristy M, Eckerman KF. Specific absorbed fractions of energy at various ages from internal photon sources. I. Methods. ORNL/TM-8381/V1 (Oak Ridge National Laboratory), April 1987.
Cloutier RJ, Smith SA, Watson EE, Snyder WS, Warner GG. Dose to the fetus from radionuclides in the bladder. Health Phys 1973;25:147–61.
Stabin MG, Siegel JA. Physical models and dose factors for use in internal dose assessment. Health Phys 2003;85:294–310.
Stabin MG, Sparks RB, Crowe E. OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 2005;46:1023–7.
Fowler JS, Ding YS, Logan J, MacGregor RR, Shea C, Garza V, et al. Species differences in [11C]clorgyline binding in brain. Nucl Med Biol 2001;28:779–85.
Lu JQ, Ichise M, Liow JS, Ghose S, Vines D, Innis RB. Biodistribution and radiation dosimetry of the serotonin transporter ligand 11C-DASB determined from human whole-body PET. J Nucl Med 2004;45:1555–9.
Tipre DN, Lu JQ, Fujita M, Ichise M, Vines D, Innis RB. Radiation dosimetry estimates for the PET serotonin transporter probe 11C-DASB determined from whole-body imaging in non-human primates. Nucl Med Commun 2004;25:81–6.
Stabin MG. MIRDOSE: personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 1996;37:538–46.
Takano A, Suhara T, Sudo Y, Inoue M, Hashimoto K, et al. Comparative evaluation of two serotonin transporter ligands in the human brain: [11C](+)McN5652 and [11C]cyanoimipramine. Eur J Nucl Med Mol Imaging 2002;29:1289–97.
Suhara T, Sudo Y, Yoshida K, Okubo Y, Fukuda H, Obata T, et al. Lung as reservoir for antidepressants in pharmacokinetic drug interactions. Lancet 1998;351:332–5.
Ding YS, Lin KS, Garza V, Carter P, Alexoff D, Logan J, et al. Evaluation of a new norepinephrine transporter PET ligand in baboons, both in brain and peripheral organs. Synapse 2003;50:345–52.
Mejia AA, Nakamura T, Masatoshi I, Hatazawa J, Masaki M, Watanuki S. Estimation of absorbed doses in humans due to intravenous administration of fluorine-18-fluorodeoxyglucose in PET studies. J Nucl Med 1991;32:699–706.
International Commission on Radiological Protection. ICRP Publication 80. Radiation dose to patients from radiopharmaceutical. Ann ICRP 1998;p 28.
Robeson W, Dhawan V, Belakhlef A, Ma Y, Pillai V, Chaly T, et al. Dosimetry of the dopamine transporter radioligand 18F-FPCIT in human subjects. J Nucl Med 2003;44:961–6.
Deterding TA, Votaw JR, Wang CK, Eshima D, Eshima L, Keil R, et al. Biodistribution and radiation dosimetry of the dopamine transporter ligand. J Nucl Med 2001;42:376–81.
Takano A, Gulyas B, Varrone A, Karlsson P, Schou M, Airaksinen A, Vandenhende F, Tauscher J, Halldin C. Imaging the norepinephrine transporter with positron emission tomography: initial human studies with (S,S)-[18F]FMeNER-D2. Eur J Nucl Med Mol Imaging 2007;48:247.
Guidance on medical exposures in medical and biomedical research. Radiation Protection 99. European Commission 1998.
Beekhuis H. Population radiation absorbed dose from nuclear medicine procedures in The Netherlands. Health Phys 1988;54:287–91.
International Commission on Radiological Protection. ICRP Publication 73.Radiological Protection and Safety in Medicine. Ann ICRP 1996;p 26.
Acknowledgements
The authors would like to thank Lilly Research Laboratories for providing the precursors and standards. We are grateful to all members of the PET group at the Karolinska Institutet. We also thank Pierre Lafolie for subject recruitment.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Takano, A., Halldin, C., Varrone, A. et al. Biodistribution and radiation dosimetry of the norepinephrine transporter radioligand (S,S)-[18F]FMeNER-D2: a human whole-body PET study. Eur J Nucl Med Mol Imaging 35, 630–636 (2008). https://doi.org/10.1007/s00259-007-0622-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-007-0622-z