Molecular Imaging of Transporters with Positron Emission Tomography

  • Gunnar AntoniEmail author
  • Jens Sörensen
  • Håkan Hall
Part of the Topics in Medicinal Chemistry book series (TMC, volume 4)


Positron emission tomography (PET) visualization of brain components in vivo is a rapidlygrowing field. Molecular imaging with PET is also increasingly used in drug development, especiallyfor the determination of drug receptor interaction for CNS-active drugs. This gives the opportunityto relate clinical efficacy to per cent receptor occupancy of a drug on a certain targetedreceptor and to relate drug pharmacokinetics in plasma to interaction with target protein. In thepresent review we will focus on the study of transporters, such as the monoamine transporters, theP-glycoprotein (Pgp) transporter, the vesicular monoamine transporter type 2, and the glucosetransporter using PET radioligands. Neurotransmitter transporters are presynaptically located andin vivo imaging using PET can therefore be used for the determination of the density of afferent neurons.Several promising PET ligands for the noradrenaline transporter (NET) have been labeled and evaluatedin vivo including in man, but a really useful PET ligand for NET still remains to be identified.The most promising tracer to date is (S,S)-[18F]FMeNER-D2.The in vivo visualization of the dopamine transporter (DAT) may give clues in the evaluation of conditionsrelated to dopamine, such as Parkinson's disease and drug abuse. The first PET radioligands basedon cocaine were not selective, but more recently several selective tracers such as [11C]PE2Ihave been characterized and shown to be suitable as PET radioligands. Although there are a largenumber of serotonin transporter inhibitors used today as SSRIs, it was not until very recently, when[11C]McN5652 was synthesized, that this transporter was studied using PET.New candidates as PET radioligands for the SERT have subsequently been developed and [11C]DASBand [11C]MADAM and their analogues are today the most promising ligands.The existing radioligands for Pgp transporters seem to be suitable tools for the study of both peripheraland central drug–Pgp interactions, although [11C]verapamil and [18F]fluoropaclitaxelare probably restricted to use in studies of the blood–brain barrier. The vesicular monoaminetransporter 2 (VMAT2) is another interesting target for diagnostic imaging and [11C]DTBZis a promising tracer. The noninvasive imaging of transporter density as a function ofdisease progression or availability following interaction with blocking drugs is highlighted, includingthe impact on both development of new therapies and the process of developing new drugs. AlthoughCNS-related work focusing on psychiatric disorders is the main focus of this review, other applicationsof PET ligands, such as diagnosis of cancer, diabetes research, and drug interactions with effluxsystems, are also discussed. The use of PET especially in terms of tracer development is brieflydescribed. Finally, it can be concluded that there is an urgent need for new, selective radioligandsfor the study of the transporter systems in the human brain using PET.

DAT NET PET Pgp Positron emission tomography SERT 


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  1. 1.
    Laakso A, Hietala J (2000) Curr Pharm Des 6:1611 CrossRefGoogle Scholar
  2. 2.
    Guilloteau D, Chalon S (2005) Curr Pharm Des 11:3237 CrossRefGoogle Scholar
  3. 3.
    Valk PE, Bailey DL, Townsend DW, Maisey MN (2003) Positron emission tomography—basic science and clinical applications. Springer, London Google Scholar
  4. 4.
    Långström B, Bergson G (1980) Radiochem Radioanal Lett 43:47 Google Scholar
  5. 5.
    Långström B, Kihlberg T, Bergström M, Antoni G, Björkman M, Forngren BH, Forngren T, Hartvig P, Markides K, Yngve U, Ögren M (1999) Acta Chem Scand 53:651 CrossRefGoogle Scholar
  6. 6.
    Antoni G, Kihlberg T, Långström B (2003) In: Vértes A, Nagy S, Klencsár Z (eds) Handbook of nuclear chemistry, vol 4. Radiochemistry and radiopharmaceutical chemistry in life sciences. Kluwer, The Netherlands, p 119 Google Scholar
  7. 7.
    Antoni G, Långström B (2003) In: Welch MJ, Redvanly CS (eds) Handbook of radiopharmaceuticals: radiochemistry and applications. Wiley, UK, p 141 Google Scholar
  8. 8.
    Logan J (2000) Nucl Med Biol 27:661 CrossRefGoogle Scholar
  9. 9.
    Patlak CS, Blasberg RG (1985) J Cereb Blood Flow Metab 5:584 CrossRefGoogle Scholar
  10. 10.
    De Hevesy G (1923) Biochem J 17:439 Google Scholar
  11. 11.
    Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2001) Adv Drug Deliv Rev 46:3 CrossRefGoogle Scholar
  12. 12.
    Waterhouse RN (2003) Mol Imaging Biol 5:376 CrossRefGoogle Scholar
  13. 13.
    Blakely RD, De Felice LJ, Hartzell HC (1994) J Exp Biol 196:263 Google Scholar
  14. 14.
    Zhou J (2004) Drugs Future 29:1235 CrossRefGoogle Scholar
  15. 15.
    Paczkowski FA, Bryan-Lluka LJ, Porzgen P, Bruss M, Bonisch H (1999) J Pharmacol Exp Ther 290:761 Google Scholar
  16. 16.
    Macey DJ, Smith HR, Nader MA, Porrino LJ (2003) J Neurosci 23:12 Google Scholar
  17. 17.
    Ding YS, Lin KS, Logan J (2006) Curr Pharm Des 12:3831 CrossRefGoogle Scholar
  18. 18.
    Owens MJ, Morgan WN, Plott SJ, Nemeroff CB (1997) J Pharmacol Exp Ther 283:1305 Google Scholar
  19. 19.
    Van Dort ME, Kim JH, Tluczek L, Wieland DM (1997) Nucl Med Biol 24:707 CrossRefGoogle Scholar
  20. 20.
    Schou M, Sovago J, Pike VW, Gulyas B, Bogeso KP, Farde L, Halldin C (2006) Mol Imaging Biol 8:1 CrossRefGoogle Scholar
  21. 21.
    McConathy J, Owens MJ, Kilts CD, Malveaux EJ, Camp VM, Votaw JR, Nemeroff CB, Goodman MM (2004) Nucl Med Biol 31:705 CrossRefGoogle Scholar
  22. 22.
    Zavidovskaia GI (1969) Zh Nevropatol Psikhiatr Im S S Korsakova 69:594 Google Scholar
  23. 23.
    Strömgren LS, Friderichsen T (1971) Nord Psykiatr Tidsskr 25:119 CrossRefGoogle Scholar
  24. 24.
    Haka MS, Kilbourn MR (1989) Int J Radiat Appl Instrum B 16:771 CrossRefGoogle Scholar
  25. 25.
    Chumpradit S, Kung MP, Panyachotipun C, Prapansiri V, Foulon C, Brooks BP, Szabo SA, Tejani-Butt S, Frazer A, Kung HF (1992) J Med Chem 35:4492 CrossRefGoogle Scholar
  26. 26.
    Wilson AA, Johnson DP, Mozley D, Hussey D, Ginovart N, Nobrega J, Garcia A, Meyer J, Houle S (2003) Nucl Med Biol 30:85 CrossRefGoogle Scholar
  27. 27.
    Logan J, Ding YS, Lin KS, Pareto D, Fowler J, Biegon A (2005) Nucl Med Biol 32:531 CrossRefGoogle Scholar
  28. 28.
    Severance AJ, Milak MS, Kumar JS, Prabhakaran J, Majo VJ, Simpson NR, Van Heertum RL, Arango V, Mann JJ, Parsey RV (2007) Eur J Nucl Med Mol Imaging 34:688 CrossRefGoogle Scholar
  29. 29.
    Ding YS, Lin KS, Garza V, Carter P, Alexoff D, Logan J, Shea C, Xu Y, King P (2003) Synapse 50:345 CrossRefGoogle Scholar
  30. 30.
    Öhman D, Norlander B, Peterson C, Bengtsson F (2001) Ther Drug Monit 23:27 CrossRefGoogle Scholar
  31. 31.
    Schou M, Halldin C, Sovago J, Pike VW, Gulyas B, Mozley PD, Johnson DP, Hall H, Innis RB, Farde L (2003) Nucl Med Biol 30:707 CrossRefGoogle Scholar
  32. 32.
    Schou M, Halldin C, Pike VW, Mozley PD, Dobson D, Innis RB, Farde L, Hall H (2005) Eur Neuropsychopharmacol 15:517 CrossRefGoogle Scholar
  33. 33.
    Schou M, Halldin C, Sovago J, Pike VW, Hall H, Gulyas B, Mozley PD, Dobson D, Shchukin E, Innis RB, Farde L (2004) Synapse 53:57 CrossRefGoogle Scholar
  34. 34.
    Hall H, Halldin C, Guilloteau D, Chalon S, Emond P, Besnard J, Farde L, Sedvall G (1999) NeuroImage 9:108 CrossRefGoogle Scholar
  35. 35.
    Hurd YL, Pristupa ZB, Herman MM, Niznik HB, Kleinman JE (1994) Neuroscience 63:357 CrossRefGoogle Scholar
  36. 36.
    Piggott MA, Marshall EF, Thomas N, Lloyd S, Court JA, Jaros E, Burn D, Johnson M, Perry RH, McKeith IG, Ballard C, Perry EK (1999) Brain 122:1449 CrossRefGoogle Scholar
  37. 37.
    Prunier C, Payoux P, Guilloteau D, Chalon S, Giraudeau B, Majorel C, Tafani M, Bezard E, Esquerre JP, Baulieu JL (2003) J Nucl Med 44:663 Google Scholar
  38. 38.
    Tissingh G, Bergmans P, Booij J, Winogrodzka A, Van Royen EA, Stoof JC, Wolters EC (1998) J Neurol 245:14 CrossRefGoogle Scholar
  39. 39.
    Shih MC, Hoexter MQ, Andrade LA, Bressan RA (2006) Sao Paulo Med J 124:168 CrossRefGoogle Scholar
  40. 40.
    Costa DC, Walker Z, Walker RW, Fontes FR (2003) Mov Disord 18(Suppl 7):S34 CrossRefGoogle Scholar
  41. 41.
    O'Brien JT, Colloby S, Fenwick J, Williams ED, Firbank M, Burn D, Aarsland D, McKeith IG (2004) Arch Neurol 61:919 CrossRefGoogle Scholar
  42. 42.
    Small GW (2004) Dement Geriatr Cogn Disord 17(Suppl 1):25 CrossRefGoogle Scholar
  43. 43.
    Sjöholm H, Bratlid T, Sundsfjord J (2004) Psychopharmacology (Berl) 173:27 CrossRefGoogle Scholar
  44. 44.
    Dean B, Hussain T (2001) Schizophr Res 52:107 CrossRefGoogle Scholar
  45. 45.
    Hsiao MC, Lin KJ, Liu CY, Tzen KY, Yen TC (2003) Schizophr Res 65:39 CrossRefGoogle Scholar
  46. 46.
    Laakso A, Bergman J, Haaparanta M, Vilkman H, Solin O, Syvälahti E, Hietala J (2001) Schizophr Res 52:115 CrossRefGoogle Scholar
  47. 47.
    Marcusson J, Eriksson K (1988) Brain Res 457:122 CrossRefGoogle Scholar
  48. 48.
    Innis R, Baldwin R, Sybirska E, Zea Y, Laruelle M, al-Tikriti M, Charney D, Zoghbi S, Smith E, Wisniewski G, Hoffer PB, Wang S, Milius RA, Neumeyer JL (1991) Eur J Pharmacol 200:369 CrossRefGoogle Scholar
  49. 49.
    Farde L, Halldin C, Müller L, Suhara T, Karlsson P, Hall H (1994) Synapse 16:93 CrossRefGoogle Scholar
  50. 50.
    Neumeyer JL, Wang SY, Gao YG, Milius RA, Kula NS, Campbell A, Baldessarini RJ, Zea-Ponce Y, Baldwin RM, Innis RB (1994) J Med Chem 37:1558 CrossRefGoogle Scholar
  51. 51.
    Benamer TS, Patterson J, Grosset DG, Booij J, De Bruin K, Van Royen E, Speelman JD, Horstink MH, Sips HJ, Dierckx RA, Versijpt J, Decoo D, Van Der Linden C, Hadley DM, Doder M, Lees AJ, Costa DC, Gacinovic S, Oertel WH, Pogarell O, Hoeffken H, Joseph K, Tatsch K, Schwarz J, Ries V (2000) Mov Disord 15:503 CrossRefGoogle Scholar
  52. 52.
    Catafau AM, Tolosa E (2004) Mov Disord 19:1175 CrossRefGoogle Scholar
  53. 53.
    Bergström KA, Halldin C, Hall H, Lundkvist C, Ginovart N, Swahn CG, Farde L (1997) Eur J Nucl Med 24:596 CrossRefGoogle Scholar
  54. 54.
    Lundkvist C, Halldin C, Ginovart N, Swahn CG, Farde L (1997) Nucl Med Biol 24:621 CrossRefGoogle Scholar
  55. 55.
    Chalon S, Garreau L, Emond P, Zimmer L, Vilar MP, Besnard JC, Guilloteau D (1999) J Pharmacol Exp Ther 291:648 Google Scholar
  56. 56.
    Guilloteau D, Emond P, Baulieu JL, Garreau L, Frangin Y, Pourcelot L, Mauclaire L, Besnard JC, Chalon S (1998) Nucl Med Biol 25:331 CrossRefGoogle Scholar
  57. 57.
    Ziebell M, Thomsen G, Knudsen GM, De Nijs R, Svarer C, Wagner A, Pinborg LH (2007) Eur J Nucl Med Mol Imaging 34:101 CrossRefGoogle Scholar
  58. 58.
    Pinborg LH, Ziebell M, Frokjaer VG, De Nijs R, Svarer C, Haugbol S, Yndgaard S, Knudsen GM (2005) J Nucl Med 46:1119 Google Scholar
  59. 59.
    Prunier C, Bezard E, Montharu J, Mantzarides M, Besnard JC, Baulieu JL, Gross C, Guilloteau D, Chalon S (2003) NeuroImage 19:810 CrossRefGoogle Scholar
  60. 60.
    Jucaite A, Odano I, Olsson H, Pauli S, Halldin C, Farde L (2006) Eur J Nucl Med Mol Imaging 33:657 CrossRefGoogle Scholar
  61. 61.
    Halldin C, Erixon-Lindroth N, Pauli S, Chou YH, Okubo Y, Karlsson P, Lundkvist C, Olsson H, Guilloteau D, Emond P, Farde L (2003) Eur J Nucl Med Mol Imaging 30:1220 CrossRefGoogle Scholar
  62. 62.
    Leroy C, Comtat C, Trebossen R, Syrota A, Martinot JL, Ribeiro MJ (2007) J Nucl Med 48:538 CrossRefGoogle Scholar
  63. 63.
    Dolle F, Emond P, Mavel S, Demphel S, Hinnen F, Mincheva Z, Saba W, Valette H, Chalon S, Halldin C, Helfenbein J, Legaillard J, Madelmont JC, Deloye JB, Bottlaender M, Guilloteau D (2006) Bioorg Med Chem 14:1115 CrossRefGoogle Scholar
  64. 64.
    Saba W, Valette H, Schollhorn-Peyronneau MA, Coulon C, Ottaviani M, Chalon S, Dolle F, Emond P, Halldin C, Helfenbein J, Madelmont JC, Deloye JB, Guilloteau D, Bottlaender M (2007) Synapse 61:17 CrossRefGoogle Scholar
  65. 65.
    Mantere T, Tupala E, Hall H, Särkioja T, Räsänen P, Bergström K, Callaway J, Tiihonen J (2002) Am J Psychiatry 159:599 CrossRefGoogle Scholar
  66. 66.
    Smith HR, Daunais JB, Nader MA, Porrino LJ (1999) Ann NY Acad Sci 877:700 CrossRefGoogle Scholar
  67. 67.
    Mukherjee J, Das MK, Yang ZY, Lew R (1998) Nucl Med Biol 25:605 CrossRefGoogle Scholar
  68. 68.
    Szabo Z, Scheffel U, Mathews WB, Ravert HT, Szabo K, Kraut M, Palmon S, Ricaurte GA, Dannals RF (1999) J Cereb Blood Flow Metab 19:967 CrossRefGoogle Scholar
  69. 69.
    Szabo Z, Kao PF, Scheffel U, Suehiro M, Mathews WB, Ravert HT, Musachio JL, Marenco S, Kim SE, Ricaurte GA et al (1995) Synapse 20:37 CrossRefGoogle Scholar
  70. 70.
    Suehiro M, Scheffel U, Ravert HT, Dannals RF, Wagner HN Jr (1993) Life Sci 53:883 CrossRefGoogle Scholar
  71. 71.
    Ichimiya T, Suhara T, Sudo Y, Okubo Y, Nakayama K, Nankai M, Inoue M, Yasuno F, Takano A, Maeda J, Shibuya H (2002) Biol Psychiatry 51:715 CrossRefGoogle Scholar
  72. 72.
    Reivich M, Amsterdam JD, Brunswick DJ, Shiue CY (2004) J Affect Disord 82:321 CrossRefGoogle Scholar
  73. 73.
    Brust P, Hinz R, Kuwabara H, Hesse S, Zessin J, Pawelke B, Stephan H, Bergmann R, Steinbach J, Sabri O (2003) Neuropsychopharmacology 28:2010 CrossRefGoogle Scholar
  74. 74.
    Kretzschmar M, Brust P, Zessin J, Cumming P, Bergmann R, Johannsen B (2003) Eur Neuropsychopharmacol 13:387 CrossRefGoogle Scholar
  75. 75.
    Reneman L, Booij J, Lavalaye J, De Bruin K, De Wolff FA, Koopmans RP, Stoof JC, Den Heeten GJ (1999) Synapse 34:77 CrossRefGoogle Scholar
  76. 76.
    Hiltunen J, Åkerman KK, Kuikka JT, Bergström KA, Halldin C, Nikula T, Räsänen P, Tiihonen J, Vauhkonen M, Karhu J, Kupila J, Lansimies E, Farde L (1998) Eur J Nucl Med 25:19 CrossRefGoogle Scholar
  77. 77.
    Ginovart N, Wilson AA, Meyer JH, Hussey D, Houle S (2001) J Cereb Blood Flow Metab 21:1342 CrossRefGoogle Scholar
  78. 78.
    Houle S, Ginovart N, Hussey D, Meyer JH, Wilson AA (2000) Eur J Nucl Med 27:1719 CrossRefGoogle Scholar
  79. 79.
    Wilson AA, Ginovart N, Hussey D, Meyer J, Houle S (2002) Nucl Med Biol 29:509 CrossRefGoogle Scholar
  80. 80.
    Meyer JH (2007) J Psychiatry Neurosci 32:86 Google Scholar
  81. 81.
    Lundquist P, Wilking H, Höglund AU, Sandell J, Bergström M, Hartvig P, Långström B (2005) Nucl Med Biol 32:129 CrossRefGoogle Scholar
  82. 82.
    Ginovart N, Wilson AA, Meyer JH, Hussey D, Houle S (2003) Synapse 47:123 CrossRefGoogle Scholar
  83. 83.
    Lundberg J, Halldin C, Farde L (2006) Synapse 60:256 CrossRefGoogle Scholar
  84. 84.
    Lundberg J, Odano I, Olsson H, Halldin C, Farde L (2005) J Nucl Med 46:1505 Google Scholar
  85. 85.
    Fang P, Shiue GG, Shimazu T, Greenberg JH, Shiue CY (2004) Appl Radiat Isot 61:1247 CrossRefGoogle Scholar
  86. 86.
    Huang Y, Hwang DR, Narendran R, Sudo Y, Chatterjee R, Bae SA, Mawlawi O, Kegeles LS, Wilson AA, Kung HF, Laruelle M (2002) J Cereb Blood Flow Metab 22:1377 CrossRefGoogle Scholar
  87. 87.
    Jarkas N, Votaw JR, Voll RJ, Williams L, Camp VM, Owens MJ, Purselle DC, Bremner JD, Kilts CD, Nemeroff CB, Goodman MM (2005) Nucl Med Biol 32:211 CrossRefGoogle Scholar
  88. 88.
    Jarkas N, McConathy J, Votaw JR, Voll RJ, Malveaux E, Camp VM, Williams L, Goodman RR, Kilts CD, Goodman MM (2005) Nucl Med Biol 32:75 CrossRefGoogle Scholar
  89. 89.
    Scherman D, Raisman R, Ploska A, Agid Y (1988) J Neurochem 50:1131 CrossRefGoogle Scholar
  90. 90.
    Kilbourn MR (1997) Nucl Med Biol 24:615 CrossRefGoogle Scholar
  91. 91.
    Batchelor M, Schenk JO (1998) J Neurosci 18:10304 Google Scholar
  92. 92.
    DaSilva JN, Carey JE, Sherman PS, Pisani TJ, Kilbourn MR (1994) Nucl Med Biol 21:151 CrossRefGoogle Scholar
  93. 93.
    Frey KA, Koeppe RA, Kilbourn MR, Vander Borght TM, Albin RL, Gilman S, Kuhl DE (1996) Ann Neurol 40:873 CrossRefGoogle Scholar
  94. 94.
    Bohnen NI, Albin RL, Koeppe RA, Wernette KA, Kilbourn MR, Minoshima S, Frey KA (2006) J Cereb Blood Flow Metab 26:1198 Google Scholar
  95. 95.
    Simpson NR, Souza F, Witkowski P, Maffei A, Raffo A, Herron A, Kilbourn M, Jurewicz A, Herold K, Liu E, Hardy MA, Van Heertum R, Harris PE (2006) Nucl Med Biol 33:855 CrossRefGoogle Scholar
  96. 96.
    Schinkel AH, Jonker JW (2003) Adv Drug Deliv Rev 55:3 CrossRefGoogle Scholar
  97. 97.
    Tan B, Piwnica-Worms D, Ratner L (2000) Curr Opin Oncol 12:450 CrossRefGoogle Scholar
  98. 98.
    Kortekaas R, Leenders KL, Van Oostrom JC, Vaalburg W, Bart J, Willemsen AT, Hendrikse NH (2005) Ann Neurol 57:176 CrossRefGoogle Scholar
  99. 99.
    Hendrikse NH, Franssen EJ, Van der Graaf WT, Vaalburg W, De Vries EG (1999) Eur J Nucl Med 26:283 CrossRefGoogle Scholar
  100. 100.
    Del Vecchio S, Ciarmiello A, Pace L, Potena MI, Carriero MV, Mainolfi C, Thomas R, D'Aiuto G, Tsuruo T, Salvatore M (1997) J Nucl Med 38:1348 Google Scholar
  101. 101.
    Sikic BI, Fisher GA, Lum BL, Halsey J, Beketic-Oreskovic L, Chen G (1997) Cancer Chemother Pharmacol 40(Suppl):S13 CrossRefGoogle Scholar
  102. 102.
    Marian T, Szabo G, Goda K, Nagy H, Szincsak N, Juhasz I, Galuska L, Balkay L, Mikecz P, Tron L, Krasznai Z (2003) Eur J Nucl Med Mol Imaging 30:1147 CrossRefGoogle Scholar
  103. 103.
    Fukumoto M, Yoshida D, Hayase N, Kurohara A, Akagi N, Yoshida S (1999) Cancer 86:1470 CrossRefGoogle Scholar
  104. 104.
    Sharma V, Beatty A, Wey SP, Dahlheimer J, Pica CM, Crankshaw CL, Bass L, Green MA, Welch MJ, Piwnica-Worms D (2000) Chem Biol 7:335 CrossRefGoogle Scholar
  105. 105.
    Sharma V (2004) Bioconjug Chem 15:1464 CrossRefGoogle Scholar
  106. 106.
    Sharma V, Prior JL, Belinsky MG, Kruh GD, Piwnica-Worms D (2005) J Nucl Med 46:354 Google Scholar
  107. 107.
    Levchenko A, Mehta BM, Lee JB, Humm JL, Augensen F, Squire O, Kothari PJ, Finn RD, Leonard EF, Larson SM (2000) J Nucl Med 41:493 Google Scholar
  108. 108.
    Bart J, Dijkers EC, Wegman TD, De Vries EG, Van der Graaf WT, Groen HJ, Vaalburg W, Willemsen AT, Hendrikse NH (2005) Br J Pharmacol 145:1045 CrossRefGoogle Scholar
  109. 109.
    Hendrikse NH, Vaalburg W (2002) Novartis Found Symp 243:137 CrossRefGoogle Scholar
  110. 110.
    Hendrikse NH, De Vries EG, Franssen EJ, Vaalburg W, Van der Graaf WT (2001) Eur J Clin Pharmacol 56:827 CrossRefGoogle Scholar
  111. 111.
    Luurtsema G, Molthoff CF, Schuit RC, Windhorst AD, Lammertsma AA, Franssen EJ (2005) Nucl Med Biol 32:87 CrossRefGoogle Scholar
  112. 112.
    Nelson WL, Olsen LD, Beitner DB, Pallow RJ Jr (1988) Drug Metab Dispos 16:184 Google Scholar
  113. 113.
    Hsiao P, Sasongko L, Link JM, Mankoff DA, Muzi M, Collier AC, Unadkat JD (2006) J Pharmacol Exp Ther 317:704 CrossRefGoogle Scholar
  114. 114.
    Bart J, Willemsen AT, Groen HJ, Van der Graaf WT, Wegman TD, Vaalburg W, De Vries EG, Hendrikse NH (2003) NeuroImage 20:1775 CrossRefGoogle Scholar
  115. 115.
    Hendrikse NH, Schinkel AH, De Vries EG, Fluks E, Van der Graaf WT, Willemsen AT, Vaalburg W, Franssen EJ (1998) Br J Pharmacol 124:1413 CrossRefGoogle Scholar
  116. 116.
    Syvänen S, Blomquist G, Sprycha M, Höglund UA, Roman M, Eriksson O, Hammarlund-Udenaes M, Långström B, Bergström M (2006) NeuroImage 32:1134 CrossRefGoogle Scholar
  117. 117.
    Sasongko L, Link JM, Muzi M, Mankoff DA, Yang X, Collier AC, Shoner SC, Unadkat JD (2005) Clin Pharmacol Ther 77:503 CrossRefGoogle Scholar
  118. 118.
    Toornvliet R, Van Berckel BN, Luurtsema G, Lubberink M, Geldof AA, Bosch TM, Oerlemans R, Lammertsma AA, Franssen EJ (2006) Clin Pharmacol Ther 79:540 CrossRefGoogle Scholar
  119. 119.
    Vogelgesang S, Cascorbi I, Schroeder E, Pahnke J, Kroemer HK, Siegmund W, Kunert-Keil C, Walker LC, Warzok RW (2002) Pharmacogenetics 12:535 CrossRefGoogle Scholar
  120. 120.
    Kurdziel KA, Kiesewetter DO, Carson RE, Eckelman WC, Herscovitch P (2003) J Nucl Med 44:1330 Google Scholar
  121. 121.
    Kiesewetter DO, Jagoda EM, Kao CH, Ma Y, Ravasi L, Shimoji K, Szajek LP, Eckelman WC (2003) Nucl Med Biol 30:11 CrossRefGoogle Scholar
  122. 122.
    Gambhir SS, Czernin J, Schwimmer J, Silverman DH, Coleman RE, Phelps ME (2001) J Nucl Med 42:1S Google Scholar
  123. 123.
    Mosconi L (2005) Eur J Nucl Med Mol Imaging 32:486 CrossRefGoogle Scholar
  124. 124.
    Di Carli MF (1998) Cardiol Rev 6:290 CrossRefGoogle Scholar
  125. 125.
    Kunkel M, Reichert TE, Benz P, Lehr HA, Jeong JH, Wieand S, Bartenstein P, Wagner W, Whiteside TL (2003) Cancer 97:1015 CrossRefGoogle Scholar
  126. 126.
    Kato H, Takita J, Miyazaki T, Nakajima M, Fukai Y, Masuda N, Fukuchi M, Manda R, Ojima H, Tsukada K, Kuwano H, Oriuchi N, Endo K (2003) Anticancer Res 23:3263 Google Scholar
  127. 127.
    Mamede M, Higashi T, Kitaichi M, Ishizu K, Ishimori T, Nakamoto Y, Yanagihara K, Li M, Tanaka F, Wada H, Manabe T, Saga T (2005) Neoplasia 7:369 CrossRefGoogle Scholar
  128. 128.
    Reske SN, Grillenberger KG, Glatting G, Port M, Hildebrandt M, Gansauge F, Beger HG (1997) J Nucl Med 38:1344 Google Scholar
  129. 129.
    Simpson IA, Carruthers A, Vannucci SJ (2007) J Cereb Blood Flow Metab Google Scholar
  130. 130.
    Vannucci SJ, Clark RR, Koehler-Stec E, Li K, Smith CB, Davies P, Maher F, Simpson IA (1998) Dev Neurosci 20:369 CrossRefGoogle Scholar
  131. 131.
    Paternostro G, Pagano D, Gnecchi-Ruscone T, Bonser RS, Camici PG (1999) Cardiovasc Res 42:246 CrossRefGoogle Scholar
  132. 132.
    Oquendo MA, Krunic A, Parsey RV, Milak M, Malone KM, Anderson A, Van Heertum RL, Mann JJ (2005) Neuropsychopharmacology 30:1163 CrossRefGoogle Scholar
  133. 133.
    Nordberg A, Lilja A, Lundqvist H, Hartvig P, Amberla K, Viitanen M, Warpman U, Johansson M, Hellstrom-Lindahl E, Bjurling P et al (1992) Neurobiol Aging 13:747 CrossRefGoogle Scholar
  134. 134.
    Kelloff GJ, Hoffman JM, Johnson B, Scher HI, Siegel BA, Cheng EY, Cheson BD, O'Shaughnessy J, Guyton KZ, Mankoff DA, Shankar L, Larson SM, Sigman CC, Schilsky RL, Sullivan DC (2005) Clin Cancer Res 11:2785 CrossRefGoogle Scholar
  135. 135.
    Dutka DP, Camici PG (2003) Heart Fail Rev 8:167 CrossRefGoogle Scholar
  136. 136.
    Landau BR, Spring-Robinson CL, Muzic RF Jr, Rachdaoui N, Rubin D, Berridge MS, Schumann WC, Chandramouli V, Kern TS, Ismail-Beigi F (2007) Am J Physiol Endocrinol Metab 293:E237 CrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  1. 1.Uppsala Imanet ABGE HealthcareUppsalaSweden
  2. 2.Uppsala Applied Science LabGE HealthcareUppsalaSweden

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