Nuclear Medicine and Biology
Volume 35, Issue 4 , Pages 447-458 , May 2008

2-(2′-((Dimethylamino)methyl)-4′-(3-[18F]fluoropropoxy)-phenylthio)benzenamine for positron emission tomography imaging of serotonin transporters

  • Julie L. Wang

      Affiliations

    • Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    • ,
  • Ajit K. Parhi

      Affiliations

    • Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    • ,
  • Shunichi Oya

      Affiliations

    • Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    • ,
  • Brian Lieberman

      Affiliations

    • Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    • ,
  • Mei-Ping Kung

      Affiliations

    • Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    • ,
  • Hank F. Kung

      Affiliations

    • Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    • Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    • Corresponding Author InformationCorresponding author. Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. Tel.: +1 215 662 3096; fax: +1 215 349 5035.

Received 19 December 2007 ,Revised 6 February 2008 ,Accepted 14 February 2008.

References 

  1. Siegel GJ. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. Philadelphia: Lippincott Williams & Wilkins; 1999;
  2. Kandel ER, Schwartz JH, Jessell TM. Principles of Neural Science. Columbus, OH: McGraw-Hill Companies; 2000;
  3. Schmitt JA, Wingen M, Ramaekers JG, Evers EA, Riedel WJ. Serotonin and human cognitive performance. Curr Pharm Des. 2006;12:2473–2486
  4. Fergusson D, Doucette S, Glass KC, Shapiro S, Healy D, Hebert P, et al. Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials. BMJ. 2005;330:396
  5. Nemeroff CB. The burden of severe depression: a review of diagnostic challenges and treatment alternatives. J Psychiatr Res. 2006;
  6. DeBattista C, Solvason HB. When the first SSRI fails: a review of switching strategies in patients resistant to an initial SSRI. Essent Psychopharmacol. 2003;5:217–224
  7. Frazer A, Morilak DA. What should animal models of depression model?. Neurosci Biobehav Rev. 2005;29:515–523
  8. Maeda J, Ji B, Irie T, Tomiyama T, Maruyama M, Okauchi T, et al. Longitudinal, quantitative assessment of amyloid, neuroinflammation, and anti-amyloid treatment in a living mouse model of Alzheimer's disease enabled by positron emission tomography. J Neurosci. 2007;27:10957–10968
  9. Koerts J, Leenders KL, Koning M, Portman AT, van Beilen M. Striatal dopaminergic activity (FDOPA-PET) associated with cognitive items of a depression scale (MADRS) in Parkinson's disease. Eur J Neurosci. 2007;25:3132–3136
  10. Bohnen NI, Gedela S, Kuwabara H, Constantine GM, Mathis CA, Studenski SA, et al. Selective hyposmia and nigrostriatal dopaminergic denervation in Parkinson's disease. J Neurol. 2007;254:84–90
  11. Swerdlow RH. PET sheds light on Alzheimer's disease genetic risk. Proc Natl Acad Sci U S A. 2007;104:18881–18882
  12. Hammoud DA, Hoffman JM, Pomper MG. Molecular neuroimaging: from conventional to emerging techniques. Radiology. 2007;245:21–42
  13. Wagner HN, Jr. Molecular imaging: thriving all over the world. J Nucl Med 2007;48:15N-16N, 19N-38N.
  14. Waterhouse RN. Determination of lipophilicity and its use as a predictor of blood–brain barrier penetration of molecular imaging agents. Mol Imaging Biol. 2003;5:376–389
  15. Huang Y, Hwang DR, Narendran R, Sudo Y, Chatterjee R, Bae SA, et al. Comparative evaluation in nonhuman primates of five PET radiotracers for imaging the serotonin transporters: [11C]McN 5652, [11C]ADAM, [11C]DASB, [11C]DAPA, and [11C]AFM. J Cereb Blood Flow Metab. 2002;22:1377–1398
  16. Szabo Z, Scheffel U, Mathews WB, Ravert HT, Szabo K, Kraut M, et al. Kinetic analysis of [11C]McN5652: a serotonin transporter radioligand. J Cereb Blood Flow Metab. 1999;19:967–981
  17. Houle S, Ginovart N, Hussey D, Meyer JH, Wilson AA. Imaging the serotonin transporter with positron emission tomography: Initial human studies with [11C]DAPP and [11C]DASB. Eur J Nucl Med. 2000;27:1719–1722
  18. Wilson AA, Ginovart N, Hussey D, Meyer J, Houle S. In vitro and in vivo characterisation of [11C]-DASB: a probe for in vivo measurements of the serotonin transporter by positron emission tomography. Nucl Med Biol. 2002;29:509–515
  19. Wilson AA, Ginovart N, Schmidt M, Meyer JH, Threlkeld PG, Houle S. Novel radiotracers for imaging the serotonin transporter by positron emission tomography: synthesis, radiosynthesis, and in vitro and ex vivo evaluation of 11C-labeled 2-(phenylthio)araalkylamines. J Med Chem. 2000;43:3103–3110
  20. Oya S, Choi SR, Hou C, Mu M, Kung MP, Acton PD, et al. 2-((2-((Dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM): an improved serotonin transporter ligand. Nucl Med Biol. 2000;27:249–254
  21. Shiue GG, Choi SR, Fang P, Hou C, Acton PD, Cardi C, et al. N,N-Dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)-benzylamine (4-(18)F-ADAM): an improved PET radioligand for serotonin transporters. J Nucl Med. 2003;44:1890–1897
  22. Huang Y, Hwang DR, Bae SA, Sudo Y, Guo N, Zhu Z, et al. A new positron emission tomography imaging agent for the serotonin transporter: synthesis, pharmacological characterization, and kinetic analysis of [11C]2-[2-(dimethylaminomethyl)phenylthio]-5-fluoromethylphenylamine ([11C]AFM). Nucl Med Biol. 2004;31:543–556
  23. Oya S, Choi SR, Coenen H, Kung HF. New PET imaging agent for the serotonin transporter: [18F]ACF (2-[(2-amino-4-chloro-5-fluorophenyl)thio]-N,N-dimethyl-benzenmethanamine). J Med Chem. 2002;45:4716–4723
  24. Zhu Z, Guo N, Narendran R, Erritzoe D, Ekelund J, Hwang DR, et al. The new PET imaging agent [11C]AFE is a selective serotonin transporter ligand with fast brain uptake kinetics. Nucl Med Biol. 2004;31:983–994
  25. Parhi AK, Wang JL, Oya S, Choi SR, Kung MP, Kung HF. 2-(2′-((Dimethylamino)methyl)-4′-(fluoroalkoxy)-phenylthio)benzenamine derivatives as serotonin transporter imaging agents. J Med Chem. 2007;50:6673–6684
  26. Brown AK, George DT, Fujita M, Liow JS, Ichise M, Hibbeln J, et al. PET [11C]DASB imaging of serotonin transporters in patients with alcoholism. Alcohol Clin Exp Res. 2007;31:28–32
  27. Cannon DM, Ichise M, Fromm SJ, Nugent AC, Rollis D, Gandhi SK, et al. Serotonin transporter binding in bipolar disorder assessed using [11C]DASB and positron emission tomography. Biol Psychiatry. 2006;60:207–217
  28. Guttman M, Boileau I, Warsh J, Saint-Cyr JA, Ginovart N, McCluskey T, et al. Brain serotonin transporter binding in non-depressed patients with Parkinson's disease. Eur J Neurol. 2007;14:523–528
  29. Ginovart N, Wilson AA, Meyer JH, Hussey D, Houle S. [11C]-DASB, a tool for in vivo measurement of SSRI-induced occupancy of the serotonin transporter: PET characterization and evaluation in cats. Synapse. 2003;47:123–133
  30. Meyer JH, Wilson AA, Sagrati S, Hussey D, Carella A, Potter WZ, et al. Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an [11C]DASB positron emission tomography study. Am J Psychiatry. 2004;161:826–835
  31. Voineskos AN, Wilson AA, Boovariwala A, Sagrati S, Houle S, Rusjan P, et al. Serotonin transporter occupancy of high-dose selective serotonin reuptake inhibitors during major depressive disorder measured with [11C]DASB positron emission tomography. Psychopharmacology (Berl). 2007;193:539–545
  32. Garg S, Thopate SR, Minton RC, Black KW, Lynch AJ, Garg PK. 3-Amino-4-(2-((4-[18F]fluorobenzyl)methylamino)methylphenylsulfanyl)benzonitrile, an F-18 fluorobenzyl analogue of DASB: synthesis, in vitro binding, and in vivo biodistribution studies. Bioconjug Chem. 2007;18:1612–1618
  33. Huang Y, Bae SA, Zhu Z, Guo N, Roth BL, Laruelle M. Fluorinated diaryl sulfides as serotonin transporter ligands: synthesis, structure-activity relationship study, and in vivo evaluation of fluorine-18-labeled compounds as PET imaging agents. J Med Chem. 2005;48:2559–2570
  34. Huang W, Huang S, Yeh C, Ma K, Wang H, Peng C, et al. 18F-ADAM PET in healthy and drug-naive depressant subjects. Washington DC J Nucl Med. 2007;48:261;Abs #1191
  35. Peng CJ, Huang YY, Huang WS, Shiue CY. An automated synthesis of N,N-dimethyl-2-(2-amino-4-[(18)F]fluorophenylthio)benzylamine (4-[(18)F]-ADAM) for imaging serotonin transporters. Appl Radiat Isot. 2008;[in Press]
  36. Oya S, Kung MP, Acton PD, Mu M, Hou C, Kung H. A new single-photon emission computed tomography imaging agent for serotonin transporters: [123I] IDAM, 5-iodo-2-((2-((dimethylamino)methyl)phenyl)thio)benzyl alcohol. J Med Chem. 1999;42:333–335
  37. Gu H, Wall SC, Rudnick G. Stable expression of biogenic amine transporters reveals differences in inhibitor sensitivity, kinetics, and ion dependence. J Biol Chem. 1994;269:7124–7130
  38. Kung MP, Hou C, Oya S, Mu M, Acton PD, Kung HF. Characterization of [123I]IDAM as a novel single-photon emission tomography tracer for serotonin transporters. Eur J Nucl Med. 1999;26:844–853
  39. Choi SR, Hou C, Oya S, Mu M, Kung MP, Siciliano M, et al. Selective in vitro and in vivo binding of [(125)I]ADAM to serotonin transporters in rat brain. Synapse. 2000;38:403–412
  40. Johnson MS, Lutz EM, Firbank S, Holland PJ, Mitchell R. Functional interactions between native Gs-coupled 5-HT receptors in HEK-293 cells and the heterologously expressed serotonin transporter. Cell Signal. 2003;15:803–811
  41. Kish SJ, Furukawa Y, Chang LJ, Tong J, Ginovart N, Wilson A, et al. Regional distribution of serotonin transporter protein in postmortem human brain: is the cerebellum a SERT-free brain region?. Nucl Med Biol. 2005;32:123–128
  42. Purselle DC, Nemeroff CB. Serotonin transporter: a potential substrate in the biology of suicide. Neuropsychopharmacology. 2003;28:613–619
  43. Surti S, Karp JS, Perkins AE, Cardi CA, Daube-Witherspoon ME, Kuhn A, et al. Imaging performance of A-PET: a small animal PET camera. IEEE Trans Med Imaging. 2005;24:844–852
  44. Huisman MC, Reder S, Weber AW, Ziegler SI, Schwaiger M. Performance evaluation of the Philips MOSAIC small animal PET scanner. Eur J Nucl Med Mol Imaging. 2007;34:532–540
  45. Battaglino R, Fu J, Spate U, Ersoy U, Joe M, Sedaghat L, et al. Serotonin regulates osteoclast differentiation through its transporter. J Bone Miner Res. 2004;19:1420–1431
  46. Bliziotes MM, Eshleman AJ, Zhang XW, Wiren KM. Neurotransmitter action in osteoblasts: expression of a functional system for serotonin receptor activation and reuptake. Bone. 2001;29:477–486
  47. Kuge Y, Minematsu K, Hasegawa Y, Yamaguchi T, Mori H, Matsuura H, et al. Positron emission tomography for quantitative determination of glucose metabolism in normal and ischemic brains in rats: an insoluble problem by the Harderian glands. J Cereb Blood Flow Metab. 1997;17:116–120
  48. Thanos PK, Taintor NB, Alexoff D, Vaska P, Logan J, Grandy DK, et al. In vivo comparative imaging of dopamine D2 knockout and wild-type mice with (11)C-raclopride and microPET. J Nucl Med. 2002;43:1570–1577
  49. Yang Y, Tai YC, Siegel S, Newport DF, Bai B, Li Q, et al. Optimization and performance evaluation of the microPET II scanner for in vivo small-animal imaging. Phys Med Biol. 2004;49:2527–2545
  50. Eckelman WC. Further discussions on choosing the number of animals for an experiment. Nucl Med Biol. 2008;35:1–2
  51. Eckelman WC, Kilbourn MR, Joyal JL, Labiris R, Valliant JF. Justifying the number of animals for each experiment. Nucl Med Biol. 2007;34:229–232
  52. Scheibe PO. Number of samples — hypothesis testing. Nucl Med Biol. 2008;35:3–9
  53. Wilson AA, Patrick Johnson D, Mozley D, Hussey D, Ginovart N, Nobrega J, et al. Synthesis and in vivo evaluation of novel radiotracers for the in vivo imaging of the norepinephrine transporter. Nucl Med Biol. 2003;30:85–92

PII: S0969-8051(08)00063-2

doi: 10.1016/j.nucmedbio.2008.02.009

Nuclear Medicine and Biology
Volume 35, Issue 4 , Pages 447-458 , May 2008

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