A PET imaging agent with fast kinetics: synthesis and in vivo evaluation of the serotonin transporter ligand [11C]2-[2-dimethylaminomethylphenylthio)]-5-fluorophenylamine ([11C]AFA)

Nuclear Medicine and Biology
Yiyun HuangMarc Laruelle

Abstract

A new serotonin transporter (SERT) ligand, [11C]2-[2-(dimethylaminomethylphenylthio)]-5-fluorophenylamine (10, [11C]AFA), was synthesized and evaluated as a candidate PET radioligand in pharmacological and pharmacokinetic studies. As a PET radioligand, AFA (8) can be labeled with either C-11 or F-18. In vitro, AFA displayed high affinity for SERT (Ki 1.46 +/- 0.15 nM) and lower affinity for norepinephrine transporter (NET, Ki 141.7 +/- 47.4 nM) or dopamine transporter (DAT, Ki > 10,000 nM). [11C]AFA (10) was prepared from its monomethylamino precursor 9 by reaction with high specific activity [11C]methyl iodide. Radiochemical yield was 43 +/- 20% based on [11C]methyl iodide at end of bombardment (EOB, n = 10) and specific activity was 2,129 +/- 1,369 Ci/mmol at end of synthesis (EOS, n = 10). Biodistribution studies in rats indicated that [11C]AFA accumulated in brain regions known to contain high concentrations of SERT. Binding in SERT-rich brain regions was reduced significantly by pretreatment with either the cold compound 8 or with the selective serotonin reuptake inhibitor (SSRI) citalopram, but not by the selective norepinephrine reuptake inhibitor nisoxetine, thus underlining its in vivo binding selectivity and specifici...Continue Reading

References

Nov 27, 1990·European Journal of Pharmacology·S M Tejani-ButtA Frazer
Sep 1, 1995·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·B SadzotD Comar
Mar 1, 1994·International Clinical Psychopharmacology·J Hyttel
May 1, 1994·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·M LaruelleP B Hoffer
Jul 1, 1993·Journal of Computer Assisted Tomography·R P WoodsS R Cherry
Jan 1, 1997·The Journal of Neuropsychiatry and Clinical Neurosciences·A Abi-DarghamJ Krystal
Aug 5, 1998·International Clinical Psychopharmacology·J F Deakin
Aug 5, 1999·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·J J Mann
Sep 9, 1999·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Z SzaboR F Dannals
Mar 4, 2000·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·A BuckC Burger
Feb 24, 2001·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·A A WilsonS Houle
Nov 20, 2002·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yiyun HuangMarc Laruelle

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Citations

Nov 6, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Peter S TalbotJulian C Matthews
Jul 9, 2010·Nuclear Medicine and Biology·Julie L WangHank F Kung
Aug 8, 2008·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·Yunhang GuoBoli Liu
Jun 16, 2011·Medicinal Research Reviews·Louise M PatersonGitte M Knudsen
Apr 11, 2009·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·D HaeuslerW Wadsak
Nov 29, 2013·Journal of Labelled Compounds & Radiopharmaceuticals·Jeffrey S Stehouwer, Mark M Goodman
Sep 17, 2008·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Benjamin L FrancBruce H Hasegawa
Jan 18, 2008·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Vibe G FrokjaerGitte M Knudsen

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