Nuclear Medicine and Biology
Volume 36, Issue 1 , Pages 17-27 , January 2009

Neuroimaging of the vesicular acetylcholine transporter by a novel 4-[18F]fluoro-benzoyl derivative of 7-hydroxy-6-(4-phenyl-piperidin-1-yl)-octahydro-benzo[1,4]oxazines

  • Dietlind Sorger

      Affiliations

    • Department of Nuclear Medicine, University of Leipzig, Leipzig 04103, Germany
    • Corresponding Author InformationCorresponding author.
    • ,
  • Matthias Scheunemann

      Affiliations

    • Institute of Interdisciplinary Isotope Research, Leipzig 04318, Germany
    • ,
  • Johnny Vercouillie

      Affiliations

    • Institute of Interdisciplinary Isotope Research, Leipzig 04318, Germany
    • ,
  • Udo Großmann

      Affiliations

    • Department of Nuclear Medicine, University of Leipzig, Leipzig 04103, Germany
    • ,
  • Steffen Fischer

      Affiliations

    • Institute of Interdisciplinary Isotope Research, Leipzig 04318, Germany
    • ,
  • Achim Hiller

      Affiliations

    • Institute of Interdisciplinary Isotope Research, Leipzig 04318, Germany
    • ,
  • Barbara Wenzel

      Affiliations

    • Institute of Interdisciplinary Isotope Research, Leipzig 04318, Germany
    • ,
  • Ali Roghani

      Affiliations

    • Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock TX 39430, USA
    • ,
  • Reinhard Schliebs

      Affiliations

    • Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig 04109, Germany
    • ,
  • Jörg Steinbach

      Affiliations

    • Institute of Interdisciplinary Isotope Research, Leipzig 04318, Germany
    • ,
  • Peter Brust

      Affiliations

    • Institute of Interdisciplinary Isotope Research, Leipzig 04318, Germany
    • ,
  • Osama Sabri

      Affiliations

    • Department of Nuclear Medicine, University of Leipzig, Leipzig 04103, Germany

Received 3 September 2008 ,Revised 7 October 2008 ,Accepted 7 October 2008.

References 

  1. Nordberg A. Nicotinic receptor abnormalities of Alzheimer's disease: therapeutic implications. Biol Psychiatry. 2001;49(3):200–210
  2. Sabri O, Kendziorra K, Wolf H, Gertz HJ, Brust P. Acetylcholine receptors in dementia and mild cognitive impairment. Eur J Nucl Med Mol Imaging. 2008;35(Suppl 1):S30–S45
  3. Gilmor ML, Counts SE, Wiley RG, Levey AI. Coordinate expression of the vesicular acetylcholine transporter and choline acetyltransferase following septohippocampal pathway lesions. J Neurochem. 1998;71:2411–2420
  4. Efange SM, von Hohenberg K, Khare AB, Tu Z, Mach RH, Parsons SM. Synthesis and biological characterization of stable and radioiodinated (+/−)-trans-2-hydroxy-3-P[4-(3-iodophenyl)piperidyl]-1,2,3,4-tetrahydronaphthalene (3′-IBVM). Nucl Med Biol. 2000;27(8):749–755
  5. Parsons SM, Bahr BA, Rogers GA, Clarkson ED, Noremberg K, Hicks BW. Acetylcholine transporter-vesamicol receptor pharmacology and structure. Progr Brain Res. 1993;98:175–181
  6. Rogers GA, Stone-Elander S, Ingvar M, Eriksson L, Parsons SM, Widen L. 18F-Labelled vesamicol derivatives: syntheses and preliminary in vivo small animal positron emission tomography evaluation. Nucl Med Biol. 1994;21(2):219–230
  7. Efange SMN, Garland EM, Staley JK, Khare AB, Mash DC. Vesicular acetylcholine transporter density and Alzheimer's disease. Neurobiol Aging. 1997;18(4):407–413
  8. Jung YW, Van Dort ME, Gildersleeve DL, Wieland DM. A radiotracer for mapping cholinergic neurons of the brain. J Med Chem. 1990;33(8):2065–2068
  9. Kilbourn MR, Jung YW, Haka MS, Gildersleeve DL, Kuhl DE, Wieland DM. Mouse brain distribution of a carbon-11 labeled vesamicol derivative: presynaptic marker of cholinergic neurons. Life Sci. 1990;47(21):1955–1963
  10. Widen L, Eriksson L, Ingvar M, Parsons SM, Rogers GA, Stone-Elander S. Positron emission tomographic studies of central cholinergic nerve terminals. Neurosci Lett. 1992;136:1–4
  11. Efange SM, Michelson RH, Khare AB, Thomas JR. Synthesis and tissue distribution of (m-[125I]iodobenzyl)trozamicol ([125I]MIBT): potential radioligand for mapping central cholinergic innervation. J Med Chem. 1993;36(12):1754–1760
  12. Jung YW, Frey KA, Mulholland GK, Del Rosario R, Sherman PS, Raffel DM, et al. Vesamicol receptor mapping of brain cholinergic neurons with radioiodine-labeled positional isomers of benzovesamicol. J Med Chem. 1996;39(17):3331–3342
  13. Mulholland GK, Wieland DM, Kilbourn MR, Frey KA, Sherman PS, Carey JE, et al. [18F]Fluoroethoxy-benzovesamicol, a PET radiotracer for the vesicular acetylcholine transporter and cholinergic synapses. Synapse. 1998;30(3):263–274
  14. Khare AB, Langason RB, Parsons SM, Mach RH, Efange SM. N-(3-Iodophenyl)trozamicol (IPHT) and related inhibitors of vesicular acetylcholine transport: synthesis and preliminary biological characterization. Nucl Med Biol. 1999;26(6):609–617
  15. Bando K, Naganuma T, Taguchi K, Ginoza Y, Tanaka Y, Koike K, et al. Piperazine analog of vesamicol: in vitro and in vivo characterization for vesicular acetylcholine transporter. Synapse. 2000;38(1):27–37
  16. Bando K, Taguchi K, Ginoza Y, Naganuma T, Tanaka Y, Koike K, et al. Synthesis and evaluation of radiolabeled piperazine derivatives of vesamicol as SPECT agents for cholinergic neurons. Nucl Med Biol. 2001;28(3):251–260
  17. Sorger D, Schliebs R, Kampfer I, Rossner S, Heinicke J, Dannenberg C, et al. In vivo [125I]-iodobenzovesamicol binding reflects cortical cholinergic deficiency induced by specific immunolesion of rat basal forebrain cholinergic system. Nucl Med Biol. 2000;27(1):23–31
  18. Emond P, Mavel S, Zea-Ponce Y, Kassiou M, Garreau L, Bodard S, et al. (E)-[125I]-5-AOIBV: a SPECT radioligand for the vesicular acetylcholine transporter. Nucl Med Biol. 2007;34(8):967–971
  19. Assaad T, Mavel S, Emond P, Chalon S, Drossard ML, Vergote J, et al. Synthesis and ex vivo evaluation of aza-trozamicol analogs as SPECT radiotracers for exploration of the vesicular acetylcholine transporter. J Lab Comp Radiopharm. 2007;50:139–145
  20. Efange SMN, Dutta AK, Michelson RH, Kung HF, Thomas JR, Billings J, et al. Radioiodinated 2-hydroxy-3-(4-iodophenyl)-1-(4-phenylpiperidinyl)propane: potential radiotracer for mapping central cholinergic innervation in vivo. Nucl Med Biol. 1992;19(3):337–348
  21. Ingvar M, Stone-Elander S, Rogers GA, Johansson B, Eriksson L, Parsons SM, et al. Striatal D2/acetylcholine interactions: PET studies of the vesamicol receptor. NeuroReport. 1993;4(12):1311–1314
  22. Mach RH, Voytko ML, Ehrenkaufer RLE, Nader MA, Tobin JR, Efange SMN, et al. Imaging of cholinergic terminals using the radiotracer [18F](+)-4-fluorobenzyltrozamicol: In vitro binding studies and positron emission tomography studies in nonhuman primates. Synapse. 1997;25(4):368–380
  23. Voytko ML, Mach RH, Gage HD, Ehrenkaufer RL, Efange SMN, Tobin JR. Cholinergic activity of aged rhesus monkeys revealed by positron emission tomography. Synapse. 2001;39(1):95–100
  24. Kawamura K, Shiba K, Tsukada H, Nishiyama S, Mori H, Ishiwata K. Synthesis and evaluation of vesamicol analog (−)-O-[11C]methylvesamicol as a PET ligand for vesicular acetylcholine transporter. Ann Nucl Med. 2006;20(6):417–424
  25. Giboureau N, Emond P, Fulton RR, Henderson DJ, Chalon S, Garreau L, et al. Ex vivo and in vivo evaluation of (2R,3R)-5-[(18)F]-fluoroethoxy-and fluoropropoxy-benzovesamicol, as PET radioligands for the vesicular acetylcholine transporter. Synapse. 2007;61(12):962–970
  26. Kuhl DE, Koeppe RA, Fessler JA, Minoshima S, Ackermann RJ, Carey JE, et al. In vivo mapping of cholinergic neurons in the human brain using SPECT and IBVM. J Nucl Med. 1993;35:405–410
  27. Kuhl DE, Minoshima S, Fessler JA, Frey KA, Foster NL, Ficaro EP, et al. In vivo mapping of cholinergic terminals in normal aging, Alzheimer's disease and Parkinson's disease. Ann Neurol. 1996;40:399–410
  28. Albin RL, Cross D, Cornblath WT, Wald JA, Wernette K, Frey KA, et al. Diminished striatal [123I]iodobenzovesamicol binding in idiopathic cervical dystonia. Ann Neurol. 2003;53(4):528–532
  29. Barret O, Mazere J, Seibyl J, Allard M. Comparison of noninvasive quantification methods of in vivo vesicular acetylcholine transporter using [(123)I]-IBVM SPECT imaging. J Cereb Blood Flow Metab. 2008;28(9):1624–1634
  30. Efange SM, Khare AB, Mach RH, Parsons SM. Hydroxylated decahydroquinolines as ligands for the vesicular acetylcholine transporter: synthesis and biological evaluation. J Med Chem. 1999;42(15):2862–2869
  31. Kilbourn MR, Hockley B, Lee L, Koeppe RA. Successful [18F]FEOBV imaging of the VAChT in monkey brain. NeuroImage. 2008;41(Suppl 2):T93
  32. Zea-Ponce Y, Mavel S, Assaad T, Kruse SE, Parsons SM, Emond P, et al. Synthesis and in vitro evaluation of new benzovesamicol analogues as potential imaging probes for the vesicular acetylcholine transporter. Bioorg Med Chem. 2005;13(3):745–753
  33. Scheunemann M, Sorger D, Kouznetsova E, Sabri O, Schliebs R, Wenzel B, et al. Sequential ring-opening of trans-1,4-cyclohexadiene dioxide for an expedient modular approach to 6,7-disubstituted (±)-hexahydro-benzo[1,4]oxazin-3-ones. Tetrahedron Lett. 2007;48:5497–5501
  34. Sorger D, Scheunemann M, Grossmann U, Fischer S, Vercouille J, Hiller A, et al. A new 18F-labeled fluoroacetylmorpholino derivative of vesamicol for neuroimaging of the vesicular acetylcholine transporter. Nucl Med Biol. 2008;35(2):185–195
  35. Roghani A, Carroll PT. Analysis of uptake and release of newly synthesized acetylcholine in PC12 cells overexpressing the rat vesicular acetylcholine transporter (VAChT). Brain Res Mol Brain Res. 2002;100(1-2):21–30
  36. Rossner S, Schliebs R, Perez-Polo JR, Wiley RG, Bigl V. Differential changes in cholinergic markers from selected brain regions after specific immunolesion of the rat cholinergic basal forebrain system. J Neurosci Res. 1995;40:31–43
  37. Brust P, Patt JT, Deuther-Conrad W, Becker G, Patt M, Schildan A, et al. In vivo measurement of nicotinic acetylcholine receptors with [18F]norchloro-fluoro-homoepibatidine. Synapse. 2008;62(3):205–218
  38. Altar CA, Marien MR. [3H]Vesamicol binding in brain: autoradiographic distribution, pharmacology, and effects of cholinergic lesions. Synapse. 1988;2:486–493
  39. Ruberg M, Mayo W, Brice A, Duyckaerts C, Hauw JJ, Simon H, et al. Choline acetyltransferase activity and [3H]vesamicol binding in the temporal cortex of patients with Alzheimer's disease, Parkinson's disease, and rats with basal forebrain lesions. Neuroscience. 1990;35(2):327–333
  40. Quinlivan M, Chalon S, Vergote J, Henderson J, Katsifis A, Kassiou M, et al. Decreased vesicular acetylcholine transporter and alpha(4)beta(2) nicotinic receptor density in the rat brain following 192 IgG-saporin immunolesioning. Neurosci Lett. 2007;415(2):97–101
  41. Weihe E, Eiden LE. Chemical neuroanatomy of the vesicular amine transporters. FASEB J. 2000;14(15):2435–2449
  42. Szymoszek A, Wenzel B, Scheunemann M, Steinbach J, Schüürmann G. First CoMFA characterization of vesamicol analogs as ligands for the vesicular acetylcholine transporter. J Med Chem. 2008;51(7):2128–2136
  43. Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. 4th ed. New York: Academic Press; 1998;
  44. Custers FGJ, Leysen JE, Stoof JC, Herscheid JDM. Vesamicol and some of its derivatives: questionable ligands for selectively labelling acetylcholine transporters in rat brain. Eur J Pharmacol. 1997;338:177–183

☆ This work was supported by a grant from Sächsisches Ministerium für Wissenschaft und Kunst, contract no. 7531.50-03-0361-01/6.

PII: S0969-8051(08)00202-3

doi: 10.1016/j.nucmedbio.2008.10.006

Nuclear Medicine and Biology
Volume 36, Issue 1 , Pages 17-27 , January 2009

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