Nuclear Medicine and Biology
Volume 33, Issue 3 , Pages 287-294 , April 2006

O-(2-[18F]fluoroethyl)-l-tyrosine: uptake mechanisms and clinical applications

  • Karl-Josef Langen

      Affiliations

    • Institute of Medicine, Research Center Jülich, D-52425 Jülich, Germany
    • Brain Imaging Center West, Research Center Jülich, D-52425 Jülich, Germany
    • Corresponding Author InformationCorresponding reviewer. Institute of Medicine, Research Center Jülich, D-52425 Jülich, FRG, Germany. Tel.: +49 2461 615900; fax: +49 2461 618261.
    • ,
  • Kurt Hamacher

      Affiliations

    • Institute of Nuclear Chemistry, Research Center Jülich, D-52425 Jülich, Germany
    • Brain Imaging Center West, Research Center Jülich, D-52425 Jülich, Germany
    • ,
  • Matthias Weckesser

      Affiliations

    • Department of Nuclear Medicine, University of Münster, D-48149 Münster, Germany
    • ,
  • Frank Floeth

      Affiliations

    • Department of Neurosurgery, Heinrich-Heine-University, D-40225 Düsseldorf, Germany
    • ,
  • Gabriele Stoffels

      Affiliations

    • Institute of Medicine, Research Center Jülich, D-52425 Jülich, Germany
    • Brain Imaging Center West, Research Center Jülich, D-52425 Jülich, Germany
    • ,
  • Dagmar Bauer

      Affiliations

    • Institute of Medicine, Research Center Jülich, D-52425 Jülich, Germany
    • Brain Imaging Center West, Research Center Jülich, D-52425 Jülich, Germany
    • ,
  • Heinz H. Coenen

      Affiliations

    • Institute of Nuclear Chemistry, Research Center Jülich, D-52425 Jülich, Germany
    • Brain Imaging Center West, Research Center Jülich, D-52425 Jülich, Germany
    • ,
  • Dirk Pauleit

      Affiliations

    • Institute of Medicine, Research Center Jülich, D-52425 Jülich, Germany
    • Brain Imaging Center West, Research Center Jülich, D-52425 Jülich, Germany

Received 30 December 2005 ,Accepted 12 January 2006.

References 

  1. Del Sole A, Falini A, Ravasi L, Ottobrini L, De Marchis D, Bombardieri E, et al. Anatomical and biochemical investigation of primary brain tumours. Eur J Nucl Med. 2001;28:1851–1872
  2. Jager PL, Vaalburg W, Pruim J, de Vries EG, Langen KJ, Piers DA. Radiolabeled amino acids: basic aspects and clinical applications in oncology. J Nucl Med. 2001;42:432–445
  3. Langen KJ, Pauleit D, Coenen HH. [123I]Iodo-α-Methyl-l-tyrosine: uptake mechanisms and clinical applications. Nucl Med Biol. 2002;29:625–631
  4. Coenen HH. Biochemistry and evaluation of fluoroamino acids. In:  Mazoyer BM,  Heiss WD,  Comar D editor. PET Studies on amino acid metabolism and protein synthesis. Dordrecht: Kluwer Academic Publishers; 1993;p. 109–129
  5. Laverman P, Boerman OC, Corstens FH, Oyen WJ. Fluorinated amino acids for tumour imaging with positron emission tomography. Eur J Nucl Med. 2002;29:681–690
  6. Wester HJ, Herz M, Weber W, Heiss P, Senekowitsch-Schmidtke R, Schwaiger M, et al. Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-l-tyrosine for tumor imaging. J Nucl Med. 1999;40:205–212
  7. Hamacher K, Coenen HH. Efficient routine production of the 18F-labelled amino acid O-(2-[18F]fluoroethyl)-l-tyrosine. Appl Radiat Isot. 2002;57:853–856
  8. Heiss P, Mayer S, Herz M, Wester HJ, Schwaiger M, Senekowitsch-Schmidtke R. Investigation of transport mechanism and uptake kinetics of O-(2-[18F]fluoroethyl)-l-tyrosine in vitro and in vivo. J Nucl Med. 1999;40:1367–1373
  9. Kaim AH, Weber B, Kurrer MO, Westera G, Schweitzer A, Gottschalk J, et al. (18)F-FDG and (18)F-FET uptake in experimental soft tissue infection. Eur J Nucl Med. 2002;29:648–654
  10. Rau FC, Philippi H, Rubio-Aliaga I, Daniel H, Weber WA, Schwaiger M, et al. Identification of subtypes of amino acid transporters in human tumor and inflammatory cells by RT-PCR. J Nucl Med. 2002;43:24;[abstract]
  11. Pauleit D, Floeth F, Herzog H, Hamacher K, Tellmann L, Muller HW, et al. Whole-body distribution and dosimetry of O-(2-[18F]fluoroethyl)-l-tyrosine. Eur J Nucl Med Mol Imaging. 2003;30:519–524
  12. Ishiwata K, Kubota K, Murakami M, Kubota R, Sasaki T, Ishii S, et al. Re-evaluation of amino acid PET studies: can the protein synthesis rates in brain and tumor tissues be measured in vivo?. J Nucl Med. 1993;34:1936–1943
  13. Pauleit D, Stoffels G, Schaden W, Hamacher K, Bauer D, Tellmann L, et al. PET with O-(2-[18F]fluoroethyl)-l-tyrosine (FET) in peripheral tumors: first clinical Results. J Nucl Med. 2005;46:411–416
  14. Hustinx R, Lemaire C, Jerusalem G, Moreau P, Cataldo D, Duysinx B, et al. Whole-body tumor imaging using PET and 2-18F-fluoro-l-tyrosine: preliminary evaluation and comparison with 18F-FDG. J Nucl Med. 2003;44:533–539
  15. Inoue T, Koyama K, Oriuchi N, Alyafei S, Yuan Z, Suzuki H, et al. Detection of malignant tumors: whole-body PET with fluorine 18 alpha-methyltyrosine versus FDG-preliminary study. Radiology. 2001;220:54–62
  16. Jager PL, Franssen EJ, Kool W, Szabo BG, Hoekstra HJ, Groen HJ, et al. Feasibility of tumor imaging using l-3-[iodine-123]-iodo-alpha-methyl-tyrosine in extracranial tumors. J Nucl Med. 1998;39:1736–1743
  17. Kanai Y, Segawa H, Miyamoto K, Uchino H, Takeda E, Endou H. Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98). J Biol Chem. 1998;273:23629–23632
  18. Pineda M, Fernandez E, Torrents D, et al. Identification of a membrane protein, LAT-2, that Co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids. J Biol Chem. 1999;274:19738–19744
  19. Babu E, Kanai Y, Chairoungdua A, et al. Identification of a novel system L amino acid transporter structurally distinct from heterodimeric amino acid transporters. J Biol Chem. 2003;278:43838–43845
  20. Rau FC, Weber WA, Wester HJ, Herz M, Becker I, Kruger A, et al. O-(2-[(18)F]Fluoroethyl)- l-tyrosine (FET): a tracer for differentiation of tumour from inflammation in murine lymph nodes. Eur J Nucl Med. 2002;29:1039–1046
  21. Mastroberardino L, Spindler B, Pfeiffer R, et al. Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family. Nature. 1998;395:288–291
  22. Shikano N, Kanai Y, Kawai K, Inatomi J, Kim do K, Ishikawa N, et al. Isoform selectivity of 3-125I-iodo-alpha-methyl-l-tyrosine membrane transport in human L-type amino acid transporters. J Nucl Med. 2003;44:244–246
  23. Lahoutte T, Caveliers V, Camargo SMR, Franca R, Ramadan T, Veljkovic E, et al. SPECT and PET amino acid tracer influx via System L (h4F2hc-hLat1) and its transstimulation. J Nucl Med. 2004;45:1591–1596
  24. Meier C, Ristic Z, Klauser S, Verrey F. Activation of system L heterodimeric amino acid exchangers by intracellular substrates. EMBO J. 2002;15(21):580–589
  25. Verrey F, Closs EI, Wagner CA, Palacin M, Endou H, Kanai Y. CATs and HATs: the SLC7 family of amino acid transporters. Pflugers Arch. 2004;447:532–542
  26. Schmidt D, Langen KJ, Herzog H, Wirths J, Holschbach M, Kiwit JC, et al. Whole body kinetics and dosimetry of l-3-[123I]iodo-alpha-methyltyrosine. Eur J Nucl Med. 1997;24:1162–1166
  27. Tang G, Wang M, Tang X, Luo L, Gan M. Pharmacokinetics and radiation dosimetry estimation of O-(2-[18F]fluoroethyl)-l-tyrosine as oncologic PET tracer. Appl Radiat Isot. 2003;58:219–225
  28. Weber WA, Wester HJ, Grosu AL, Herz M, Dzewas B, Feldmann HJ, et al. O-(2-[18 F]Fluoroethyl)-l-tyrosine and l-[methyl-11C]methionine uptake in brain tumours: initial results of a comparative study. Eur J Nucl Med. 2000;27:542–549
  29. Weckesser M, Langen KJ, Rickert CH, Kloska S, Straeter R, Hamacher K, et al. Initial experiences with O-(2-[18F]fluoroethyl)-l-tyrosine PET in the evaluation of primary brain tumors. Eur J Nucl Med. 2005;32:422–429
  30. DeAngelis LM. Brain tumors. N Engl J Med. 2001;344:114–123
  31. Jansen EP, Dewit LG, van Herk M, Bartelink H. Target volumes in radiotherapy for high-grade malignant gliomas of the brain. Radiother Oncol. 2000;56:151–156
  32. Watanabe M, Tanaka R, Takeda N. Magnetic resonance imaging and histopathology of cerebral gliomas. Neuroradiology. 1992;34:463–469
  33. Mosskin M, Ericson K, Hindmarsh T, von Holst H, Collins VP, Bergström M, et al. Positron emission tomography compared with magnetic resonance imaging and computed tomography in supratentorial gliomas using multiple stereotactic biopsies as reference. Acta Radiol. 1989;30:225–232
  34. Ogawa T, Shishido F, Kanno I, Inugami A, Fujita H, Murakami M, et al. Cerebral Glioma: evaluation with Methionine PET. Radiology. 1993;186:45–53
  35. Herholz K, Holzer T, Bauer B, Schroder R, Voges J, Ernestus RI, et al. 11C-methionine PET for differential diagnosis of low-grade gliomas. Neurology. 1998;50:1316–1322
  36. Ribom D, Eriksson A, Hartman M, Engler H, Nilsson A, Langstrom B, et al. Positron emission tomography (11)C-methionine and survival in patients with low-grade gliomas. Cancer. 2001;92:1541–1549
  37. Goldman S, Levivier M, Pirotte B, Brucher JM, Wikler D, Damhaut P, et al. Regional glucose metabolism and histopathology of gliomas. A study based on positron emission tomography-guided stereotactic biopsy. Cancer. 1996;78:1098–1106
  38. Levivier M, Massager N, Wikler D, Lorenzoni J, Ruiz S, Devriendt D, et al. Use of stereotactic PET images in dosimetry planning of radiosurgery for brain tumors: clinical experience and proposed classification. J Nucl Med. 2004;45:1146–1154
  39. Pauleit D, Floeth F, Tellmann L, Hamacher K, Hautzel H, Müller HW, et al. Comparison of O-(2-[18F]fluoroethyl)-l-tyrosine (FET) PET and 3-[123I]iodo-α-methyl-l-tyrosine (IMT) SPECT in brain tumors. J Nucl Med. 2004;45:374–381
  40. Messing-Jünger MJ, Floeth FW, Pauleit D, Reifenberger G, Willing R, Gärtner J, et al. Multimodal target point assessment for atereotactic biopsy in children with diffuse bithalamic astrocytomas. Childs Nerv Syst. 2002;18:445–449
  41. Pauleit D, Floeth F, Hamacher K, Riemenschneider MJ, Reifenberger G, Müller HW, et al. O-(2-[18F]fluoroethyl)-l-tyrosine PET combined with magnetic resonance imaging improves the diagnostic assessment of cerebral gliomas. Brain. 2005;128:678–687
  42. Pöpperl G, Gotz C, Rachinger W, Gildehaus FJ, Tonn JC, Tatsch K. Value of O-(2-[18F]fluoroethyl)- l-tyrosine PET for the diagnosis of recurrent glioma. Eur J Nucl Med Mol Imaging. 2004;31:1464–1470
  43. Langen KJ, Jarosch M, Muhlensiepen H, Hamacher K, Broer S, Jansen P, et al. Comparison of fluorotyrosines and methionine uptake in F98 rat gliomas. Nucl Med Biol. 2003;30:501–508
  44. Floeth F, Pauleit D, Langen KJ, Reifenberger G, Stoffels G, Stummer W, et al. Differentiation of tumorous and non-tumorous ring enhancing lesions (REL) with FET-PET. J Nucl Med. 2006;47:[in press]
  45. Floeth F, Pauleit D, Wittsack HJ, Langen KJ, Reifenberger G, Hamacher K, et al. Multimodal metabolic imaging of cerebral gliomas using positron emission tomography with [18F]-fluoroethyl-l-tyrosine and magnetic resonance spectroscopy. J Neurosurg. 2005;102:318–327
  46. Spaeth N, Wyss MT, Weber B, Scheidegger S, Lutz A, Verwey J, et al. Uptake of 18F-fluorocholine, 18F-fluoroethyl-l-tyrosine, and 18F-FDG in acute cerebral radiation injury in the rat: implications for separation of radiation necrosis from tumor recurrence. J Nucl Med. 2004;45:1931–1938
  47. Pöpperl G, Goldbrunner R, Gildehaus FJ, Kreth FW, Tanner P, Holtmannspotter M, et al. O-(2-[(18)F]fluoroethyl)-l-tyrosine PET for monitoring the effects of convection-enhanced delivery of paclitaxel in patients with recurrent glioblastoma. Eur J Nucl Med Mol Imaging. 2005;32:1018–1025
  48. Rachinger W, Goetz C, Popperl G, Gildehaus FJ, Kreth FW, Holtmannspotter M, et al. Positron emission tomography with O-(2-[18F]fluoroethyl)-l-tyrosine versus magnetic resonance imaging in the diagnosis of recurrent gliomas. Neurosurgery. 2005;57:505–511
  49. Kole AC, Pruim J, Nieweg OE, van Ginkel RJ, Hoekstra HJ, Schraffordt H, et al. PET with l-[1-carbon-11]-tyrosine to visualize tumors and measure protein synthesis rates. J Nucl Med. 1997;38:191–195
  50. Pauleit D, Zimmermann A, Stoffels G, Bauer D, Risse J, Flüss J, et al. FET PET compared with FDG PET and CT in patients with head-neck cancers. J Nucl Med. 2006;47:256–261

PII: S0969-8051(06)00009-6

doi: 10.1016/j.nucmedbio.2006.01.002

Nuclear Medicine and Biology
Volume 33, Issue 3 , Pages 287-294 , April 2006

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