Nuclear Medicine and Biology
Volume 35, Issue 8 , Pages 825-837 , November 2008

In vivo imaging of vesicular monoamine transporter 2 in pancreas using an 18F epoxide derivative of tetrabenazine

  • Hank F. Kung

      Affiliations

    • Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
    • Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA
    • Corresponding Author InformationCorresponding author. Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA. Tel.: +1 215 662 3989; fax: +1 215 349 5035.
    • ,
  • Brian P. Lieberman

      Affiliations

    • Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
    • ,
  • Zhi-Ping Zhuang

      Affiliations

    • Avid Radiopharmaceuticals, Inc., Philadelphia, PA 19104, USA
    • ,
  • Shunichi Oya

      Affiliations

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

      Affiliations

    • Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
    • ,
  • Seok Rye Choi

      Affiliations

    • Avid Radiopharmaceuticals, Inc., Philadelphia, PA 19104, USA
    • ,
  • Karl Poessl

      Affiliations

    • Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
    • ,
  • Eric Blankemeyer

      Affiliations

    • Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
    • ,
  • Catherine Hou

      Affiliations

    • Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA
    • ,
  • Daniel Skovronsky

      Affiliations

    • Avid Radiopharmaceuticals, Inc., Philadelphia, PA 19104, USA
    • ,
  • Michael Kilbourn

      Affiliations

    • Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA

Received 30 May 2008 ,Revised 20 August 2008 ,Accepted 31 August 2008.

References 

  1. Li H, Waites CL, Staal RG, Dobryy Y, Park J, Sulzer DL, et al. Sorting of vesicular monoamine transporter 2 to the regulated secretory pathway confers the somatodendritic exocytosis of monoamines. Neuron. 2005;48:619–633
  2. Anlauf M, Eissele R, Schafer MK, Eiden LE, Arnold R, Pauser U, et al. Expression of the two isoforms of the vesicular monoamine transporter (VMAT1 and VMAT2) in the endocrine pancreas and pancreatic endocrine tumors. J Histochem Cytochem. 2003;51:1027–1040
  3. Souza F, Freeby M, Hultman K, Simpson N, Herron A, Witkowsky P, et al. Current progress in non-invasive imaging of beta cell mass of the endocrine pancreas. Curr Med Chem. 2006;13:2761–2773
  4. Bertuzzi F, Marzorati S, Secchi A. Islet cell transplantation. Curr Mol Med. 2006;6:369–374
  5. Briones RM, Miranda JM, Mellado-Gil JM, Castro MJ, Gonzalez-Molina M, Cuesta-Munoz AL, et al. Differential analysis of donor characteristics for pancreas and islet transplantation. Transplant Proc. 2006;38:2579–2581
  6. Frank AM, Barker CF, Markmann JF. Comparison of whole organ pancreas and isolated islet transplantation for type 1 diabetes. Adv Surg. 2005;39:137–163
  7. Iwanaga Y, Matsumoto S, Okitsu T, Noguchi H, Nagata H, Yonekawa Y, et al. Living donor islet transplantation, the alternative approach to overcome the obstacles limiting transplant. Ann N Y Acad Sci. 2006;1079:335–339
  8. Pileggi A, Cobianchi L, Inverardi L, Ricordi C. Overcoming the challenges now limiting islet transplantation: a sequential, integrated approach. Ann N Y Acad Sci. 2006;1079:383–398
  9. Sherr J, Sosenko J, Skyler JS, Herold KC. Prevention of type 1 diabetes: the time has come. Nat Clin Pract Endocrinol Metab. 2008;
  10. Hampe CS, Wallen AR, Schlosser M, Ziegler M, Sweet IR. Quantitative evaluation of a monoclonal antibody and its fragment as potential markers for pancreatic beta cell mass. Exp Clin Endocrinol Diabetes. 2005;113:381–387
  11. Markmann JF, Deng S, Desai NM, Huang X, Velidedeoglu E, Frank A, et al. The use of non-heart-beating donors for isolated pancreatic islet transplantation. Transplantation. 2003;75:1423–1429
  12. Sweet IR, Cook DL, Lernmark A, Greenbaum CJ, Krohn KA. Non-invasive imaging of beta cell mass: a quantitative analysis. Diabetes Technol Ther. 2004;6:652–659
  13. Schneider S, Feilen PJ, Schreckenberger M, Schwanstecher M, Schwanstecher C, Buchholz HG, et al. In vitro and in vivo evaluation of novel glibenclamide derivatives as imaging agents for the non-invasive assessment of the pancreatic islet cell mass in animals and humans. Exp Clin Endocrinol Diabetes. 2005;113:388–395
  14. Sweet IR, Cook DL, Lernmark A, Greenbaum CJ, Wallen AR, Marcum ES, et al. Systematic screening of potential beta-cell imaging agents. Biochem Biophys Res Commun. 2004;314:976–983
  15. Jakobsen AM, Andersson P, Saglik G, Andersson E, Kolby L, Erickson JD, et al. Differential expression of vesicular monoamine transporter (VMAT) 1 and 2 in gastrointestinal endocrine tumours. J Pathol. 2001;195:463–472
  16. Weihe E, Schafer MK, Erickson JD, Eiden LE. Localization of vesicular monoamine transporter isoforms (VMAT1 and VMAT2) to endocrine cells and neurons in rat. J Mol Neurosci. 1994;5:149–164
  17. Anlauf M, Schafer MK, Schwark T, von Wurmb-Schwark N, Brand V, Sipos B, et al. Vesicular monoamine transporter 2 (VMAT2) expression in hematopoietic cells and in patients with systemic mastocytosis. J Histochem Cytochem. 2006;54:201–213
  18. Bohnen NI, Albin RL, Koeppe RA, Wernette KA, Kilbourn MR, Minoshima S, et al. Positron emission tomography of monoaminergic vesicular binding in aging and Parkinson disease. J Cereb Blood Flow Metab. 2006;26:1198–1212
  19. Kilbourn MR. In vivo radiotracers for vesicular neurotransmitter transporters. Nucl Med Biol. 1997;24:615–619
  20. Koeppe RA, Frey KA, Vander Borght TM, Karlamangla A, Jewett DM, Lee LC, et al. Kinetic evaluation of and [11C]dihydrotetrabenazine by dynamic PET: measurement of vesicular monoamine transporter. J Cereb Blood Flow Metab. 1996;16:1288–1299
  21. Harris PE, Ferrara C, Barba P, Polito T, Freeby M, Maffei A. VMAT2 gene expression and function as it applies to imaging beta-cell mass. J Mol Med. 2008;86:5–16
  22. Maffei A, Liu Z, Witkowski P, Moschella F, Del Pozzo G, Liu E, et al. Identification of tissue-restricted transcripts in human islets. Endocrinology. 2004;145:4513–4521
  23. Raffo A, Hancock K, Polito T, Xie Y, Andan G, Witkowski P, et al. Role of vesicular monoamine transporter type 2 in rodent insulin secretion and glucose metabolism revealed by its specific antagonist tetrabenazine. J Endocrinol. 2008;198:41–49
  24. Simpson NR, Souza F, Witkowski P, Maffei A, Raffo A, Herron A, et al. Visualizing pancreatic beta-cell mass with [(11)C]DTBZ. Nucl Med Biol. 2006;33:855–864
  25. Souza F, Simpson N, Raffo A, Saxena C, Maffei A, Hardy M, et al. Longitudinal noninvasive PET-based beta cell mass estimates in a spontaneous diabetes rat model. J Clin Invest. 2006;116:1506–1513
  26. Kung MP, Hou C, Goswami R, Ponde DE, Kilbourn MR, Kung HF. Characterization of optically resolved 9-fluoropropyl-dihydrotetrabenazine as a potential PET Imaging agent targeting vesicular monoamine transporters. Nucl Med Biol. 2007;34:239–246
  27. Goswami R, Ponde DE, Kung MP, Hou C, Kilbourn MR, Kung HF. Fluoroalkyl derivatives of dihydrotetrabenazine as positron emission tomography imaging agents targeting vesicular monoamine transporters. Nucl Med Biol. 2006;33:685–694
  28. Kung MP, Hou C, Lieberman BP, Oya S, Ponde DE, Blankemeyer E, et al. In vivo imaging of {beta}-cell mass in rats using 18F-FP-(+)-DTBZ: a potential PET ligand for studying diabetes mellitus. J Nucl Med. 2008;49:1171–1176
  29. Morisseau C, Hammock BD. Gerry Brooks and epoxide hydrolases: four decades to a pharmaceutical. Pest Manag Sci. 2008;64:594–609
  30. Morisseau C, Newman JW, Wheelock CE, Hill Iii T, Morin D, Buckpitt AR, et al. Development of metabolically stable inhibitors of mammalian microsomal epoxide hydrolase. Chem Res Toxicol. 2008;21:951–957
  31. Chiamvimonvat N, Ho CM, Tsai HJ, Hammock BD. The soluble epoxide hydrolase as a pharmaceutical target for hypertension. J Cardiovasc Pharmacol. 2007;50:225–237
  32. Scherman D, Raisman R, Ploska A, Agid Y. [3H]Dihydrotetrabenazine, a new in vitro monoaminergic probe for human brain. J Neurochem. 1988;50:1131–1136
  33. Surti S, Karp JS, Perkins AE, Cardi CA, DAube-Witherspoon MW, Kuhn A, et al. Imaging performance of A-PET: a small animal PET camera. IEEE Trans Med Imaging. 2005;24:844–852
  34. Davis R, Kluge AF, Maddox ML, Sparacino ML. Synthesis of spiro[1,3,4,6,7,11b-hexahydro-2H-benzo[a]quinolizine-2,2′-oxiranes] and spiro[1,3,4,6,7,11b-hexahydro-2H-benzo[a]quinolizine-2,5′oxazolidin-2′-ones] and the use of carbon-13 nuclear magnetic resonance spectroscopy in the assignment of stereochemistry to epoxides. J Org Chem. 1983;48:255–259
  35. Kilbourn MR, Lee LC, Heeg MJ, Jewett DM. Absolute configuration of (+)-alpha-dihydrotetrabenazine, an active metabolite of tetrabenazine. Chirality. 1997;9:59–62
  36. Kilbourn M, Sherman P. In vivo binding of (+)-[alpha]-[3H]dihydrotetrabenazine to the vesicular monoamine transporter of rat brain: bolus vs. equilibrium studies. Eur J Pharmacol. 1997;331:161–168
  37. Kandel ER, Schwartz JH, Jessell TM. Principles of Neural Science. New York: McGraw-Hill Companies; 2000;
  38. Kung MP, Kung HF. Mass effect of injected dose in small rodent imaging by SPECT and PET. Nucl Med Biol. 2005;32:673–678
  39. Eckelman WC, Kilbourn MR, Mathis CA. Discussion of targeting proteins in vivo: in vitro guidelines. Nucl Med Biol. 2006;33:449–451
  40. Eckelman WC, Mathis CA. Molecular targets. Nucl Med Biol. 2006;33:1
  41. Eckelman WC, Frank JA, Brechbiel M. Theory and practice of imaging saturable binding sites. Invest Radiol. 2002;37:101–106

PII: S0969-8051(08)00179-0

doi: 10.1016/j.nucmedbio.2008.08.004

Nuclear Medicine and Biology
Volume 35, Issue 8 , Pages 825-837 , November 2008

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