Molecular Imaging of Tumor Metabolism and Apoptosis

  • U. Haberkorn
  • A. Altmann
  • W. Mier
  • M. Eisenhut
Conference paper
Part of the Ernst Schering Foundation Symposium Proceedings book series (SCHERING FOUND, volume 2007/4)


Increased metabolism has been found to be one of the most prominent features of malignant tumors. This property led to the development of tracers for the assessment of glucose metabolism and amino acid transport and their application for tumor diagnosis and staging. Prominent examples are fluorodeoxyglucose, methionine and tyrosine analogs, which have found broad clinical application. Since quantitative procedures are available, these techniques can also be used for therapy monitoring. Another approach may be based on the noninvasive detection of apoptosis with tracers for phosphatidyl-serine presentation and/or caspase activation as surrogate markers for therapeutic efficacy. Finally, the evaluation of hypoxia with nitroimidazoles may be a valuable tool for prognosis and therapy planning.


Amino Acid Transport Protein Synthesis Rate Herpes Simplex Virus Thymidine Kinase Intracellular Substrate Amino Acid Transport System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Ahuja V, Coleman RE, Herndon J, Patz EF (1998) Prognostic significance of FDG-PET imaging in patients with non-small cell lung cancer. Cancer 83:918–924PubMedGoogle Scholar
  2. Amano S, Inoue T, Tomiyoshi K et al (1998) In vivo comparison of PET and SPECT radiopharmaceuticals in detecting breast cancer. J Nucl Med 39:1424–1427PubMedGoogle Scholar
  3. Bassa P, Kim EE, Inoue T, Wong FC, Korkmaz M, Yang DJ, Hicks KW, Buzdar AU, Podoloff DA (1996) Evaluation of preoperative chemotherapy using PET with fluorine-18-fluorodeoxyglucose in breast cancer. J Nucl Med 37:931–938PubMedGoogle Scholar
  4. Bauer C, Bauder-Wuest U, Mier W, Haberkorn U, Eisenhut M (2005) 131I-labeled peptides as caspase substrates for apoptosis imaging. J Nucl Med 46:1066–1074PubMedGoogle Scholar
  5. Bergstrom M, Collins VP, Ehrin E et al (1983) Discrepancies in brain tumor extent as shown by computed tomography and positron emission tomography using [68Ga]EDTA, [11C]glucose, and [11C]methionine. J Comput Assist Tomogr 7:1062–1066PubMedGoogle Scholar
  6. Bergstrom M, Muhr C, Lundberg PO et al (1987) Rapid decrease in amino acid metabolism in prolactin-secreting pituitary adenomas after bromocriptine treatment: a PET study. J Comput Assist Tomogr 11:815–819PubMedGoogle Scholar
  7. Berra E, Benizri E, Ginouves A, Volmat V, Roux D, Pouyssegur J (2003) HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. EMBO J 22:4082–4090PubMedGoogle Scholar
  8. Blankenberg FG, Katsikis PD, Tait JF, Davis RE, Naumovski L, Ohtsuki K et al (1998) In vivo detection and imaging of phosphatidylserine expression during programmed cell death. Proc Natl Acad Sci U S A 95:6349–6354PubMedGoogle Scholar
  9. Blankenberg FG, Katsikis PD, Tait JF, Davis RE, Naumovski L, Ohtsuki K et al (1999) Imaging of apoptosis (programmed cell death) with 99mTc annexin V. J Nucl Med 40:184–191PubMedGoogle Scholar
  10. Boerner P, Saier MH (1985) Adaptive regulatory control of system A transport activity in a kidney epithelial cell line (MDCK) and in a transformed variant. J Cell Physiol 122:308–315PubMedGoogle Scholar
  11. Bos R, van Der Hoeven JJ, van Der Wall E, van der Groep P, van Diest PJ, Comans EFI, Joshi U, Semenza GL, Hoekstra OS, Lammertsma AA, Molthoff CFM (2002) Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. J Clin Oncol 20:379–387PubMedGoogle Scholar
  12. Brown RS, Leung JY, Kison PV, Zasadny KR, Flint A, Wahl RL (1999) Glucose transporters and FDG uptake in untreated primary human non-small cell lung cancer. J Nucl Med 40:556–565PubMedGoogle Scholar
  13. Busch H, Davis JR, Honig GR et al (1959) The uptake of a variety of amino acids into nuclear proteins of tumors and other tissues. Cancer Res 19:1030–1039PubMedGoogle Scholar
  14. Christensen HN (1990) Role of amino acid transport and countertransport in nutrition and metabolism. Physiol Rev 70:43–76PubMedGoogle Scholar
  15. Daemen BJ, Elsinga PH, Mooibroek J et al (1991) PET measurements of hyperthermia-induced suppression of protein synthesis in tumors in relation to effects on tumor growth. J Nucl Med 32:1587–1592PubMedGoogle Scholar
  16. DeBoer JR, vander Laan BFAM, Oruim J et al (2002) Carbon-11 tyrosine PET for visualization and protein synthesis rate assessment of laryngeal and hypopharyngeal carcinomas. Eur J Nucl Med 29:1182–1187Google Scholar
  17. Dimitrakopoulou-Strauss A, Strauss LG, Burger C (2001) Quantitative PET studies in pretreated melanoma patients: a comparison of 6-[18F]fluoro-L-DOPA with 18F-FDG and 15O-water using compartment and noncompartment analysis. J Nucl Med 42:248–256PubMedGoogle Scholar
  18. Duhaylongsod FG, Lowe VJ, Patz EF Jr, Vaughn AL, Coleman RE, Wolfe WG (1995) Lung tumor growth correlates with glucose metabolism measured by fluoride-18 fluorodeoxyglucose positron emission tomography. Ann Thorac Surg 60:1348–1352PubMedGoogle Scholar
  19. Dunzendorfer U, Schmall B, Bigler RE et al (1981) Synthesis and body distribution of alpha-aminoisobutyric acid-L-11C in normal and prostate cancer bearing rat after chemotherapy. Eur J Nucl Med 6:535–538PubMedGoogle Scholar
  20. Dwamena BA, Sonnad SS, Angobaldo JO, Wahl RL (1999) Metastases from non-small cell lung cancer: mediastinal staging in the 1990s – meta-analytic comparison of PET and CT. Radiology 213:530–536PubMedGoogle Scholar
  21. Erler JT, Cawthorne CJ, Williams KJ et al (2004) Hypoxia-mediated down-regulation of Bid and Bax in tumors occurs via hypoxia inducible factor 1-dependent and -independent mechanisms and contributes to drug resistance. Mol Cell Biol 24:2875–2889PubMedGoogle Scholar
  22. Flier JS, Mueckler MM, Usher P, Lodish HF (1987) Elevated levels of glucose transport and transporter messenger RNA are induced by ras or src oncogenes. Science 235:1492–1495PubMedGoogle Scholar
  23. Graeber TG, Osmanian C, Jacks T et al (1996) Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumors. Nature 379:88–91PubMedGoogle Scholar
  24. Grönroos T, Bentzen L, Marjamäki P, Murata R, Horsman MR, Keiding S, Eskola O, Haaparanta M, Minn H, Solin O (2004) Comparison of the biodistribution of two hypoxia markers [18F]FETNIM and [18F]FMISO in an experimental mammary carcinoma. Eur J Nucl Med Mol Imaging 31:513–520PubMedGoogle Scholar
  25. Haberkorn U, Eisenhut M (2005) Molecular imaging and therapy – a programme based on the development of new biomolecules. Eur J Nucl Med Mol Imaging 32:1354–1359PubMedGoogle Scholar
  26. Haberkorn U, Strauss LG, Dimitrakopoulou A, Engenhart R, Oberdorfer F, Ostertag H, Romahn J, van Kaick G (1991) PET studies of fluorodeoxyglucose metabolism in patients with recurrent colorectal tumors receiving radiotherapy. J Nucl Med 32:1485–1490PubMedGoogle Scholar
  27. Haberkorn U, Reinhardt M, Strauss LG, Oberdorfer F, Berger MR, Altmann A, Wallich R, Dimitrakopoulou A, van Kaick G (1992) Metabolic design of combination therapy: use of enhanced fluorodeoxyglucose uptake caused by chemotherapy. J Nucl Med 33:1981–1987PubMedGoogle Scholar
  28. Haberkorn U, Strauss LG, Dimitrakopoulou A et al (1993) Fluorodeoxyglucose imaging of advanced head and neck cancer after chemotherapy. J Nucl Med 34:12–17PubMedGoogle Scholar
  29. Haberkorn U, Ziegler SI, Oberdorfer F, Trojan H et al (1994) FDG uptake, tumor proliferation and expression of glycolysis associated genes in animal tumor models. Nucl Med Biol 21:827–834PubMedGoogle Scholar
  30. Haberkorn U, Altmann A, Morr I et al (1997a) Multi tracer studies during gene therapy of hepatoma cells with HSV thymidine kinase and ganciclovir. J Nucl Med 38:1048–1054PubMedGoogle Scholar
  31. Haberkorn U, Bellemann ME, Altmann A, Gerlach L, Morr I, Oberdorfer F, Brix G, Doll J, Blatter J, Kaick G van (1997b) PET 2-fluoro-2-deoxyglucose uptake in rat prostate adenocarcinoma during chemotherapy with gemcitabine. J Nucl Med 38:1215–1221PubMedGoogle Scholar
  32. Haberkorn U, Bellemann ME, Gerlach L, Morr I, Trojan H, Brix G, Altmann A, Doll J, van Kaick G (1998) Uncoupling of 2-fluoro-2-deoxyglucose transport and phosphorylation in rat hepatoma during gene therapy with HSV thymidine kinase. Gene Ther 5:880–887PubMedGoogle Scholar
  33. Haberkorn U, Altmann A, Kamencic H, Morr I, Traut U, Henze M, Jiang S, Metz J, Kinscherf R (2001a) Glucose transport and apoptosis after gene therapy with HSV thymidine kinase. Eur J Nucl Med 28:1690–1696PubMedGoogle Scholar
  34. Haberkorn U, Bellemann ME, Brix G, Kamencic H, Morr I, Traut U, Altmann A, Doll J, Blatter J, Kinscherf R (2001b) Apoptosis and changes in glucose transport early after treatment of Morris hepatoma with gemcitabine. Eur J Nucl Med 28:418–425PubMedGoogle Scholar
  35. Haberkorn U, Kinscherf R, Krammer PH, Mier W, Eisenhut M (2001c) Investigation of a potential scintigraphic marker of apoptosis: radioiodinated Z-Val-Ala-DL-Asp(O-Methyl)-fluoromethyl ketone. Nucl Med Biol 28:793–798PubMedGoogle Scholar
  36. Haberkorn U, Altmann A, Eisenhut M (2002) Functional genomics and proteomics – the role of nuclear medicine. Eur J Nuc Med 29:115–132Google Scholar
  37. Haberkorn U, Mier W, Eisenhut M (2005) Scintigraphic imaging of gene expression and gene transfer. Curr Med Chem 12:779–794PubMedGoogle Scholar
  38. Haddad JJ (2002) Oxygen-sensing mechanisms and the regulation of redox-responsive transcription factors in development and pathophysiology. Respir Res 3:26PubMedGoogle Scholar
  39. Hayes N, Biswas C, Strout HV, Berger J (1993) Activation by protein synthesis inhibitors of glucose transport into L6 muscle cells. Biochem Biophys Res Commun 190:881–887PubMedGoogle Scholar
  40. Heesters MA, Go KG, Kamman RL et al (1998) 11C-tyrosine positron emission tomography and 1H magnetic resonance spectroscopy of the response of brain gliomas to radiotherapy. Neuroradiology 40:103–108PubMedGoogle Scholar
  41. Heiss P, Mayer S, Herz M et al (1999) Investigation of transport mechanism and uptake kinetics of O-(2-[18F]fluoroethyl)-L-tyrosine in vitro and in vivo. J Nucl Med 40:1367–1373PubMedGoogle Scholar
  42. Herholz K, Holzer T, Bauer B et al (1998) 11C-methionine PET for differential diagnosis of low-grade gliomas. Neurology 50:1316–1322PubMedGoogle Scholar
  43. Hewitson KS, McNeill LA, Riordan MV et al (2002) Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family. J Biol Chem 277:26351–26355PubMedGoogle Scholar
  44. Higashi K, Clavo AC, Wahl RL (1993) In vitro assessment of 2-fluoro-2-deoxy-D-glucose, L-methionine and thymidine as agents to monitor the early response of a human adenocarcinoma cell line to radiotherapy. J Nucl Med 34:773–779PubMedGoogle Scholar
  45. Higashi K, Ueda Y, Yagishita M et al (2000) FDG PET measurement of the proliferative potential of non-small cell lung cancer. J Nucl Med 41:85–92PubMedGoogle Scholar
  46. Hughes CS, Shen JW, Subjeck JR (1989) Resistance to etoposide induced by three glucose-regulated stresses in Chinese hamster ovary cells. Cancer Res 49:4452–4454PubMedGoogle Scholar
  47. Inoue T, Shibasaki T, Oriuchi N et al (1999) 18F alpha-methyl tyrosine PET studies in patients with brain tumors. J Nucl Med 40:399–405PubMedGoogle Scholar
  48. Ishiwata K, Hatazawa J, Kubota K et al (1989) Metabolic fate of L-[methyl-11C]methionine in human plasma. Eur J Nucl Med 15:665–669PubMedGoogle Scholar
  49. Ishiwata K, Kubota K, Kubota R et al (1991) Selective 2-[18F]fluorodopa uptake for melanogenesis in murine metastatic melanoma. J Nucl Med 32:95–101PubMedGoogle Scholar
  50. Ishiwata K, Hatazawa J, Kubota K et al (1996) A feasibility study on L-[1-carbon11]tyrosine and L-[methyl-carbon-11]methionine to assess liver protein synthesis. J Nucl Med 37:279–285PubMedGoogle Scholar
  51. Isselbacher KJ (1972) Sugar and amino acid transport by cells in culture: differences between normal and malignant cells. N Engl J Med 286:929–933PubMedGoogle Scholar
  52. Jager PL, Plaat BE, deVries EG et al (2000) Imaging of soft tissue tumors using L-3-[iodine-123]iodo-alpha-methyl-tyrosine SPECT: comparison with proliferative and mitotic activity, cellularity and vascularity. Clin Cancer Res 6:2252–2259PubMedGoogle Scholar
  53. Jager PL, Vaalburg W, Pruim J et al (2001) Radiolabeled amino acids: basic aspects and clinical applications in oncology. J Nucl Med 42:432–445PubMedGoogle Scholar
  54. Jansson T, Westlin JE, Ahlstrom H et al (1995) Positron emission tomography studies in patients with locally advanced and/or metastatic breast cancer: a method for early therapy evaluation. J Clin Oncol 13:1470–1477PubMedGoogle Scholar
  55. Kaschten B, Stevenaert A, Sadzot B et al (1998) Preoperative evaluation of 54 gliomas by PET with fluorine-18-fluorodeoxyglucose and/or carbon-11-methionine. J Nucl Med 39:778–785PubMedGoogle Scholar
  56. Kubota K, Matsuzawa T, Fujiwara T et al (1989) Differential diagnosis of AH109A tumor and inflammation by radioscintigraphy with L-[methyl-11C]-methionine. Jpn J Cancer Res 80:778–782PubMedGoogle Scholar
  57. Kubota K, Matsuzawa T, Fujiwara T et al (1990) Differential diagnosis of lung tumor with positron emission tomography: a prospective study. J Nucl Med 31:1927–1932PubMedGoogle Scholar
  58. Kuwert T, Probst-Cousin S, Woesler B et al (1997) Iodine-123-alpha-methyl tyrosine in glioma: correlation with cellular density and proliferative activity. J Nucl Med 38:1551–1555PubMedGoogle Scholar
  59. Lando D, Peet DJ, Gorman JJ, Whelan DA, Whitelaw ML, Bruick RK (2002a) FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev 16:1466–1471PubMedGoogle Scholar
  60. Lando D, Peet DJ, Whelan DA, Gorman JJ, Whitelaw ML (2002b) Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science 295:858–861PubMedGoogle Scholar
  61. Langen KJ, Coenen HH, Roosen N et al (1990) SPECT studies of brain tumors with L-3-[123I] iodo-alpha-methyl tyrosine: comparison with PET, 124IMT and first clinical results. J Nucl Med 31:281–286PubMedGoogle Scholar
  62. Langen KJ, Ziemons K, Kiwit JC et al (1997) 3-[123I]iodo-alpha-methyltyrosine and [methyl-11C]-L-methionine uptake in cerebral gliomas: a comparative study using SPECT and PET. J Nucl Med 38:517–522PubMedGoogle Scholar
  63. Lee ST, Scott AM (2007) Hypoxia positron emission tomography imaging with 18F-Fluoromisonidazole. Semin Nucl Med 37:451–461PubMedGoogle Scholar
  64. Leskinen-Kallio S, Lindholm P, Lapela M et al (1994) Imaging of head and neck tumors with positron emission tomography and [11C]methionine. Int J Radiat Oncol Biol Phys 30:1195–1199PubMedGoogle Scholar
  65. Lindholm P, Leskinen S, Lapela M (1998) Carbon-11-methionine uptake in squamous cell head and neck cancer. J Nucl Med 39:1393–1397PubMedGoogle Scholar
  66. Martin SJ, Reutelingsperger CPM, McGahon AJ (1995) Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J Exp Med 182:1545–1556PubMedGoogle Scholar
  67. McConathy J, Martarello L, Malveaux EJ et al (2002) Radiolabeled amino acids for tumor imaging with PET: radiosynthesis and biological evaluation of 2-amino-3-[18F]fluoro-2-methylpropanoic acid and 3-[18F]fluoro-2-methyl-2-(methylamino)propanoic acid. J Med Chem 45:2240–2249PubMedGoogle Scholar
  68. Mosskin M, Bergstrom M, Collins VP et al (1986) Positron emission tomography with 11C-methionine of intracranial tumors compared with histology of multiple biopsies. Acta Radiol 369 Suppl:157–160Google Scholar
  69. Ogawa T, Kanno I, Shishido F et al (1991) Clinical value of PET with 18F-fluorodeoxyglucose and L-methyl-11C-methionine for diagnosis of recurrent brain tumor and radiation injury. Acta Radiol 32:197–202PubMedGoogle Scholar
  70. Ogawa T, Shishido F, Kanno I et al (1993) Cerebral glioma: evaluation with methionine PET. Radiology 186:45–53PubMedGoogle Scholar
  71. Padhani AR, Krohn KA, Lewis JS, Alber M (2007) Imaging oxygenation of human tumors. Eur Radiol 17:861–872PubMedGoogle Scholar
  72. Plaat B, Kole A, Mastik M et al (1999) Protein synthesis rate measured with L-[1-11C]tyrosine positron emission tomography correlated with mitotic activity and MIB-1 antibody-detected proliferation in human soft tissue sarcomas. Eur J Nucl Med 26:328–332PubMedGoogle Scholar
  73. Plate KH, Breier G, Weich HA, Risau W (1992) Vascular endothelial growth factor is a potential tumor angiogenesis factor in human gliomas in vivo. Nature 359:845–848PubMedGoogle Scholar
  74. Rau FC, Weber WA, Wester HJ et al (2002) O-(2-[18F]fluoroethyl)-L-tyrosine (FET): a tracer for differentiation of tumor from inflammation in murine lymph nodes. Eur J Nucl Med 29:1039–1046Google Scholar
  75. Reske SN, Kotzerke J (2001) FDG-PET for clinical use results of the 3rd German Interdisciplinary Consensus Conference, “Onko-PET III”, 21 July and 19 September 2000. Eur J Nucl Med 28:1707–1723PubMedGoogle Scholar
  76. Rodriguez M, Rehn S, Ahstrom H et al (1995) Predicting malignancy grade with PET in non-Hodgkin's lymphoma. J Nucl Med 36:1790–1796PubMedGoogle Scholar
  77. Rozental JM, Levine RL, Nickles RJ, Dobkin JA (1989) Glucose uptake by gliomas after treatment. A positron emission tomographic study. Arch Neurol 46:1302–1307PubMedGoogle Scholar
  78. Saier MH, Daniels JR, Boerner P, Lin J (1988) Animal amino acid transport systems in animal cells: potential targets of oncogene action and regulators of cellular growth. J Membr Biol 104:1–20PubMedGoogle Scholar
  79. Scanlon K, Safirstein RL, Thies H et al (1983) Inhibition of amino acid transport by cis-diaminedichloroplatinum (II) derivatives L1210 murine leukemia cells. Cancer Res 43:4211–4215PubMedGoogle Scholar
  80. Scanlon K, Cashmore AR, Kashani-Sabet M et al (1987) Inhibition of methionine uptake by methotrexate in mouse leukemia L1210. Cancer Chemother Pharmacol 19:21–24PubMedGoogle Scholar
  81. Schaider H, Haberkorn U, Berger MR et al (1996) Application of alpha-aminoisobutyric acid, L-methionine, thymidine and 2-fluoro-2-deoxy-D-glucose to monitor effects of chemotherapy in a human colon carcinoma cell line. Eur J Nucl Med 23:55–60PubMedGoogle Scholar
  82. Schwarzbach M, Willeke F, Dimitrakopoulou-Strauss A et al (1999) Functional imaging and detection of local recurrence in soft tissue sarcomas by positron emission tomography. Anticancer Res 19:1343–1349PubMedGoogle Scholar
  83. Semenza GL (2002) HIF-1 and tumor progression: pathophysiology and therapeutics. Trends Mol Med 8:S62–S67PubMedGoogle Scholar
  84. Shawver LK, Olson SA, White MK, Weber MJ (1987) Degradation and biosynthesis of the glucose transporter protein in chicken embryo fibroblasts transformed by the src oncogene. Mol Cell Biol 7:2112–2118PubMedGoogle Scholar
  85. Shoup TM, Olson J, Hoffman JM et al (1999) Synthesis and evaluation of [18F]1-amino-3-fluorocyclobutane-1-carboxylic acid to image brain tumors. J Nucl Med 40:331–338PubMedGoogle Scholar
  86. Sieger S, Jiang S, Schönsiegel F, Eskerski H, Kübler W, Altmann A, Haberkorn U (2003) Tumor-specific activation of the sodium/iodide symporter gene under control of the glucose transporter gene 1 promoter (GTI-1.3). Eur J Nucl Med Mol Imaging 30:748–756PubMedGoogle Scholar
  87. Sieger S, Jiang S, Kleinschmidt J, Eskerski H, Schönsiegel F, Altmann A, Mier W, Haberkorn U (2004) Tumor-specific gene expression using regulatory elements of the glucose transporter isoform 1 gene. Cancer Gene Ther 11:41–51PubMedGoogle Scholar
  88. Singh D, Banerji AK, Dwarakanath BS, Tripathi RP, Gupta JP, Mathew TL, Ravindranath T, Jain V (2005) Optimizing cancer radiotherapy with 2-deoxy-d-glucose dose escalation studies in patients with glioblastoma multiforme. Strahlenther Onkol 181:507–514PubMedGoogle Scholar
  89. Stadler P, Becker A, Feldmann HJ et al (1999) Influence of the hypoxic subvolume on the survival of patients with head and neck cancer. Int J Radiat Oncol Biol Phys 44:749–754PubMedGoogle Scholar
  90. Teicher BA (2004) Hypoxia and drug resistance. Cancer Metastasis Rev 13:139–168Google Scholar
  91. Uehara H, Miyagawa T, Tjuvajev J et al (1997) Imaging experimental brain tumors with 1-aminocyclopentane carboxylic acid and alpha-aminoisobutyric acid: comparison to fluorodeoxyglucose and diethylenetriaminepentaacetic acid in morphologically defined tumor regions. J Cereb Blood Flow Metab 17:1239–1253PubMedGoogle Scholar
  92. Vaalburg W, Coenen HH, Crouzel C et al (1992) Amino acids for the measurement of protein synthesis in vivo by PET. Int J Rad Appl Instrum B 19:227–237PubMedGoogle Scholar
  93. Vansteenkiste JF, Stroobants SG, Dupont PJ et al (1999) Prognostic importance of the standardized uptake value on (18)F-fluoro-2-deoxy-glucose-positron emission tomography scan in non-small-cell lung cancer: an analysis of 125 cases. Leuven Lung Cancer Group. J Clin Oncol 17:3201–3206PubMedGoogle Scholar
  94. Villa P, Kaufmann SH, Earnshaw WC (1997) Caspases and caspase inhibitors. Trends Biochem Sci 22:388–393PubMedGoogle Scholar
  95. Weber WA, Wester HJ, Herz M et al (2001) Kinetics of F-18-fluoroethyl-L-tyrosine (FET) in patients with brain tumors. J Nucl Med 42:214P–215PGoogle Scholar
  96. Wertheimer E, Sasson S, Cerasi E, Ben-Neriah Y (1991) The ubiquitous glucose transporter GLUT-1 belongs to the glucose-regulated protein family of stress-inducible proteins. Proc Natl Acad Sci U S A 88:2525–2529PubMedGoogle Scholar
  97. Wester HJ, Herz M, Weber W et al (1999) Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor imaging. J Nucl Med 40:205–212PubMedGoogle Scholar
  98. Widnell CC, Baldwin SA, Davies A, Martin S, Pasternak CA (1990) Cellular stress induces a redistribution of the glucose transporter. FASEB J 4:1634–1637PubMedGoogle Scholar
  99. Wienhard K, Herholz K, Coenen HH et al (1991) Increased amino acid transport into brain tumors measured by PET of L-(2-18F)fluorotyrosine. J Nucl Med 32:1338–1346PubMedGoogle Scholar
  100. Willemsen AT, vanWaarde A, Paans AM et al (1995) In vivo protein synthesis rate determination in primary or recurrent brain tumors using L-[1-11C]-tyrosine and PET. J Nucl Med 36:411–419PubMedGoogle Scholar
  101. Wurker M, Herholz K, Voges J et al (1996) Glucose consumption and methionine uptake in low-grade gliomas after iodine-125 brachytherapy. Eur J Nucl Med 23:583–586PubMedGoogle Scholar
  102. Young SD, Marshall RS, Hill RP (1988) Hypoxia induces DNA overreplication and enhances metastatic potential of murine tumor cells. Proc Natl Acad Sci U S A 85:9533–9537PubMedGoogle Scholar
  103. Zwaal RFA, Schroit AJ (1997) Pathophysiologic implications of membrane phospholipid asymmetry in blood cells. Blood 89:1121–1132PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • U. Haberkorn
    • 1
  • A. Altmann
    • 1
  • W. Mier
    • 1
  • M. Eisenhut
    • 2
  1. 1.Department of Nuclear MedicineUniversity of HeidelbergHeidelbergGermany
  2. 2.Department of Radiopharmaceutical ChemistryDKFZHeidelbergGermany

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