Metabolic functional imaging for tumor radiosensitivity monitoring

Critical Reviews in Oncology/Hematology

Volumn 62, Issue 3, 2007, Pages 227-239

  Belkacémi, Yazid ^a   Tsoutsou, Pelagia ^b   Magné, Nicolas ^c   Castadot, Pierre ^d   Azria, David ^e  

^a UNIV LILLE   (France)

^b Department of Radiation Oncology   (Greece)

^c Department of Radiotherapy   (France)

^d Jules Bordet Anti Cancer Institute   (Belgium)

^e CENTRE VAL D AURELLE   (France)

Author keywords

Nuclear imaging; PET; Radiation therapy; Radiosensitivity; Tumor response

Indexed keywords

CANCER GROWTH FACTOR; DEOXYURIDINE; FLUORODEOXYGLUCOSE F 18; IODINE 123; METHIONINE C 11; METHOXY ISOBUTYL ISONITRILE TECHNETIUM TC 99M; RADIOPHARMACEUTICAL AGENT; THYMIDINE; TRACER; TYROSINE;

APOPTOSIS; CANCER RADIOTHERAPY; CELL PROLIFERATION; ESOPHAGUS CANCER; HEAD AND NECK CANCER; HUMAN; HYPOXIA; IMAGE ANALYSIS; ISOTOPE LABELING; MALIGNANT NEOPLASTIC DISEASE; METABOLISM; NONHUMAN; POSITRON EMISSION TOMOGRAPHY; RADIATION DOSE; RADIATION RESPONSE; RADIOSENSITIVITY; REVIEW; SQUAMOUS CELL CARCINOMA; TISSUE OXYGENATION; TREATMENT RESPONSE; TUMOR VASCULARIZATION; UTERINE CERVIX CANCER;

HUMANS; NEOPLASMS; POSITRON-EMISSION TOMOGRAPHY; PREDICTIVE VALUE OF TESTS; RADIATION TOLERANCE; RADIOISOTOPES; RADIOTHERAPY; TOMOGRAPHY, EMISSION-COMPUTED, SINGLE-PHOTON;

EID: 34247850828     PISSN: 10408428     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.critrevonc.2006.12.002     Document Type: Review

References (111)

1. Ross G.M. Induction of cell death by radiotherapy. Endocr Relat Cancer 6 (1999) 41-44
2. Martin F., and Solary E. Tumor cell resistance to DNA-damaging agents: from apoptosis to neioisis. Curr Med Chem Anti-Cancer Agents 4 (2004) 461-463
3. Joiner M.C., Lambin P., Malaise E.P., et al. Hypersensitivity to very low single radiation doses: its relationship to the adaptive response and induced radioresistance. Mutat Res 358 (1996) 171-183
4. Lambin P., Malaise E.P., and Joiner M.C. Might intrinsic radioresistance of human tumour cells be induced by radiation?. Int Radiat Biol 69 (1996) 279-290
5. Skov K.A. Radioresponsiveness at low doses: hyper-radiosensitivity and increased radioresistance in mammalian cells. Mutat Res 430 (1999) 241-253
6. Fornace A., Fuchs Z., Weichselbaum R.R., et al. Radiation therapy. In: Mendelsohn J., Howley P.M., Israel M.A., and Liotta L.A. (Eds). The molecular basis of cancer (2001), WB Sanders, Philadelphia 423-454
7. Bristow R.G., and Hill R.P. Molecular and cellular basis of radiotherapy. In: Tannock I.F., and Hill R.P. (Eds). The basis science of oncology. 3rd ed. (1987), McGraw-Hill, New York 295-321
8. Van de Wiele C., Lahorte C., Oyen W., et al. Nuclear medicine imaging to predict response to radiotherapy: a review. Int J Radiat Oncol Biol Phys 55 (2003) 5-15
9. Collier T.L., Lecomte R., McCarthy T.J., et al. Assessment of cancer-associated biomarkers by positron emission tomography: advances and challenges. Dis Markers 18 (2002) 211-217
10. Brahme A. Biologically optimized 3-dimensional in vivo predictive assay-based radiation therapy using positron emission tomography-computerized tomography imaging. Acta Oncol 42 (2003) 123-136
11. Stahl A., Wieder H., Piert M., et al. Positron emission tomography as a tool for translational research in oncology. Mol Imaging Biol 6 (2004) 214-224
12. Brady F., Luthra S.K., Brown G.D., et al. Radiolabelled tracers and anticancer drugs for assessment of therapeutic efficacy using PET. Curr Pharm Des 18 (2001) 1863-1892
13. Solomon B., McArthur G., Cullinane C., et al. Applications of positron emission tomography in the development of molecular targeted cancer therapeutics. Bio Drugs 17 (2003) 339-354
14. Mendelsohn M.L. The growth fraction: a new concept applied to tumors. Science 132 (1960) 1496-1503
15. Slingerland J.M., and Tannock I.F. Cell proliferation and cell death. In: Tannock I.F., and Hill R.P. (Eds). The basic science of oncology. 3rd ed. (1987), McGraw-Hill, New York 134-165
16. Couturier O., Luxen A., Chatal J.F., et al. Fluorinated tracers for imaging cancer with positron emission tomography. Eur J Nucl Med Mol Imaging 31 (2004) 1182-1206
17. Rigo P., Paulus P., Kaschten B.J., et al. Oncological applications of positron emission tomography with fluorine-18 fluorodeoxyglucose. Eur J Nucl Med 23 (1996) 1641-1674
18. Weber W.A. Use of PET for monitoring cancer therapy and for predicting outcome. J Nucl Med 46 (2005) 983-995
19. Wieder H.A., Brucher B.L., Zimmermann F., et al. Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment. J Clin Oncol 22 (2004) 900-908
20. Ott K., Fink U., Becker K., et al. Prediction of response to preoperative chemotherapy in gastric carcinoma by metabolic imaging: results of a prospective trial. J Clin Oncol 21 (2003) 4604-4610
21. Hicks R.J., MacManus M.P., Matthews J.P., et al. Early FDG-PET imaging after radical radiotherapy for non-small-cell lung cancer: inflammatory changes in normal tissues correlate with tumor response and do not confound therapeutic response evaluation. Int J Radiat Oncol Biol Phys 60 (2004) 412-418
22. Brun E., Ohlsson T., Erlandsson K., et al. Early prediction of treatment outcome in head and neck cancer with 2-(18)FDG PET. Acta Oncol 36 (1997) 741-747
23. Rege S., Safa A.A., Chaiken L., et al. Positron emission tomography: an independant indicator of radiocurability in head an neck carcinoma. Am J Clin Oncol Cancer Clin Trials 23 (2000) 164-169
24. Allal A.S., Dulguerov P., Allaoua M., et al. Standardized uptake value of 2-[F-18]fluoro-2-deoxy-d-glucose in predicting outcome in head and neck carcinomas treated by radiotherapy with or without chemotherapy. J Clin Oncol 20 (2002) 1398-1404
25. Kalff V., Duong C., Drummond E.G., et al. Findings on 18F-FDG PET scans after neoadjuvant chemoradiation provides prognostic stratification in patients with locally advanced rectal carcinoma subsequently treated by radical surgery. J Nucl Med 47 (2006) 14-22
26. Beitler J.J. Mirror, mirror on the wall which is the greatest predictive assay of them all?. Int J Radiat Oncol Biol Phys 59 (2004) 1272-1273
27. Juweid M.E., and Cheson B.D. Positron-emission tomography and assessment of cancer therapy. N Engl J Med 354 (2006) 496-497
28. Schelling M., Avril N., Nahrig J., et al. Positron emission tomography using [(18)F] fluorodeoxyglucose for monitoring primary chemotherapy in breast cancer. J Clin Oncol 18 (2000) 1689-1695
29. Smith I.C., Welch A.E., Hutcheon A.W., et al. Positron emission tomography using [(18)F]-fluorodeoxy-d-glucose to predict the pathologic response of breast cancer to primary chemotherapy. J Clin Oncol 18 (2000) 1676-1688
30. Weber W.A., Ott K., Becker K., et al. Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J Clin Oncol 19 (2001) 3058-3065
31. Kostakoglu L., Coleman M., Leonard J.P., et al. PET predicts prognosis after one cycle of chemotherapy in aggressive lymphoma and Hodgkin's disease. J Nucl Med 43 (2002) 1018-1027
32. Spaepen K., Stroobants S., Dupont P., et al. Early restaging positron emission tomography with (18)F-fluorodeoxyglucose predicts outcome in patients with aggressive non-Hodgkin's lymphoma. Ann Oncol 13 (2002) 1356-1363
33. Findlay M., Young H., Cunningham D., et al. Noninvasive monitoring of tumor metabolism using fluorodeoxyglucose and positron emission tomography in colorectal cancer liver metastases: correlation with tumor response to fluorouracil. J Clin Oncol 14 (1996) 700-708
34. Weber W.A., PETersen V., Schmidt B., et al. Positron emission tomography in non-small-cell lung cancer: prediction of response to chemotherapy by quantitative assessment of glucose use. J Clin Oncol 21 (2003) 2651-2657
35. Brun E., Kjellen E., Tennvall J., et al. FDG PET studies during treatment: prediction of therapy outcome in head and neck squamous cell carcinoma. Head Neck 24 (2002) 127-135
36. Kostakoglu L., Leonard J.P., Coleman M., et al. The role of FDG-PET imaging in the management of lymphoma. Clin Adv Hematol Oncol 2 (2004) 115-121
37. Kostakoglu L., and Goldsmith S.J. PET in the assessment of therapy response in patients with carcinoma of the head and neck and of the esophagus. J Nucl Med 45 (2004) 56-68
38. Brücher BL, Becker K, Lordick F, et al. Clinical impact of assessment of histopathological response by residual tumor cell quantification in patients with neoadjuvant treated esophageal squamous cell carcinomas (ESCC). ASCO Gastrointestinal Cancer Symposium 2006 [Abstract].
39. Minn H., Lapela M., Klemi P.J., et al. Prediction of survival with fluorine-18-fluoro-deoxyglucose and PET in head and neck cancer. J Nucl Med 38 (1997) 1907-1911
40. Bos R., van Der Hoeven J.J., van Der Wall E., et al. Biologic correlates of (18) fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. J Clin Oncol 20 (2002) 379-387
41. 18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. Eur J Cancer 35 (1999) 1773-1782
42. 11C-methionine positron emission tomography and proliferating cell nuclear antigen staining. Neurosurg Rev 22 (1999) 210-214
43. Lindholm P., Leskinen S., and Lapela M. Carbone-11-methionine uptake in squamous cell head and neck cancer. J Nucl Med 39 (1998) 1393-1397
44. 11C]tyrosine and 2-[F-18]fluoro-2-deoxy-d-glucose. Int J Rad Appl Instrum B 18 (1991) 503-511
45. Inoue T., Tomiyoshi K., Higuichi T., et al. Biodistribution studies on l-3-[fluorine-18]fluoro-alpha-methyl tyrosine: a potential tumor-detecting agent. J Nucl Med 39 (1998) 663-667
46. Shields A.F., Larson S.M., Grunbaum Z., et al. Short term thymidine uptake in normal and neoplastic tissues: studies for PET. J Nucl Med 25 (1984) 759-764
47. Mankoff D.A., Dehdashti F., and Shields A.F. Characterizing tumors using metabolic imaging: PET imaging for cellular proliferation and steroid receptors. Neoplasia 2 (2000) 71-88
48. 124I] iododeoxyuridine. Cancer Res 60 (2000) 624-635
49. Gudjonssona O., Bergstrom M., Kristjansson S., et al. Analysis of Br-76-BrdU in DNA of brain tumors after a Pet study does not support its use as a proliferative marker. Nucl Med Biol 28 (2001) 59-65
50. Lehtio K., Eskola O., Viljanen T., et al. Imaging perfusion and hypoxia with PET to predict radiotherapy response in head-and-neck cancer. Int J Radiat Oncol Biol Phys 59 (2004) 971-982
51. Chapman J.D., Schneider R.F., Urbain J.L., et al. Single-photon emission computed tomography and positron-emission tomography assays for tissue oxygenation. Semin Radiat Oncol 11 (2001) 47-57
52. Lewis J.S., and Welch M.J. PET imaging of hypoxia. Q J Nucl Med 45 (2001) 183-188
53. Bentzen L., Keiding S., Horsman M.R., et al. Feasibility of detecting hypoxia in experimental mouse tumours with 18F-fluorinated tracers and positron emission tomography-a study evaluating [18F]fluoro-2-deoxy-d-glucose. Acta Oncol 39 (2000) 629-637
54. Dubois L., Landuyt W., Haustermans K., et al. Evaluation of hypoxia in an experimental rat tumour model by [(18)F]fluoromisonidazole PET and immunohistochemistry. Br J Cancer 91 (2004) 1947-1954
55. Foo S.S., Abbott D.F., Lawrentschuk N., et al. Functional imaging of intratumoral hypoxia. Mol Imaging Biol 6 (2004) 291-305
56. Evans S.M., Kachur A.V., Shiue C.Y., et al. Noninvasive detection of tumor hypoxia using the 2-nitroimidazole [18F]EF1. J Nucl Med 41 (2000) 327-336
57. Koh W.J., Rasey J.S., Evans M.L., et al. Imaging of hypoxia in human tumors with (F-18) fluoromisonidasole. Int J Radiat Oncol Biol Phys 22 (1992) 199-212
58. Rasey J.S., Koh W.J., Evans M.L., et al. Quantifying regional hypoxia in human tumors with positron emission tomography of (F-18) fluoromisonidasole: a pretherapy study of 37 patients. Int J Radiat Oncol Biol Phys 36 (1996) 417-428
59. Sorger D., Patt M., Kumar P., et al. [18F] fluoroazomycinarabinofuranoside (18FAZA) and [18F]fluoromisonidazole (18FMISO): a comparative study of their selective uptake in hypoxic cells and PET imaging in experimental rat tumors. Nucl Med Biol 30 (2003) 317-326
60. Barthel H., Wilson H., Collingridge D.R., et al. In vivo evaluation of [18F]fluoroetanidazole as a new marker for imaging tumour hypoxia with positron emission tomography. Br J Cancer 90 (2004) 2232-2242
61. Zanzonico P., O'Donoghue J., Chapman J.D., et al. Iodine-124-labeled iodo-azomycin-galactoside imaging of tumor hypoxia in mice with serial microPET scanning. Eur J Nucl Med Mol Imaging 31 (2004) 117-128
62. 2O. J Nucl Med 45 (2004) 1851-1859
63. Rajendran J.G., Mankoff D.A., O'Sullivan F., et al. Hypoxia and glucose metabolism in malignant tumors: evaluation by [18F]fluoromisonidazole and [18F]fluorodeoxyglucose positron emission tomography imaging. Clin Cancer Res 10 (2004) 2245-2252
64. Rajendran J.G., and Krohn K.A. Imaging hypoxia and angiogenesis in tumors. Radiol Clin North Am 43 (2005) 169-187
65. Wen B., Burgman P., Zanzonico P., et al. A preclinical model for noninvasive imaging of hypoxia-induced gene expression; comparison with an exogenous marker of tumor hypoxia. Eur J Nucl Med Mol Imaging 31 (2004) 1530-1538
66. Urtasun R.C., Parliament M.B., McEwan A.J., et al. Measurement of hypoxia in human tumors by non-invasive SPECT imaging of iodoazomycin arabinoside. Br J Cancer 74 (1996) 209-212
67. Lehtio K., Oikonen V., Gronroos T., et al. Imaging of blood flow and hypoxia in head and neck cancer: initial evaluation with [(15)O]H(2)O and [(18) F]fluoroerythronitroimidazole PET. J Nucl Med 42 (2001) 1643-1652
68. Meyn R.L., Milas L., and Stephens L.C. Apoptosis in tumor biology and therapy. Adv Exp Med Biol 400 (1997) 657-667
69. Scott N., Hale A., Deakin M., et al. A histopathological assessment of the response of rectal adenocarcinoma to combination chemo- radiotherapy: relationship to apoptotic activity, p53 and bcl-2 expression. Eur J Surg Oncol 24 (1998) 169-173
70. Rodel C., Grabenbauer G.G., Papadopoulos T., et al. Apoptosis as a cellular predictor for histopathologic response to neoadjuvant radiochemotherapy in patients with rectal cancer. Int J Radiat Oncol Biol Phys 52 (2002) 294-303
71. Abe T., Sakaguchi Y., Ohno S., et al. Apoptosis and p53 overexpression in human rectal cancer; relationship with response to hyperthermo-chemo-radiotherapy. Anticancer Res 21 (2001) 2115-2120
72. Lara P.C., Perez S., Rey A., et al. Apoptosis in carcinoma of the bladder. Relation with radiation treatment results. Int J Radiat Oncol Biol Phys 43 (1999) 1015-1019
73. Rodel C., Grabenbauer G.G., Rodel F., et al. Apoptosis, p53, bcl-2, and Ki-67 in invasive bladder carcinoma: possible predictors for response to radiochemotherapy and successful bladder preservation. Int J Radiat Oncol Biol Phys 6 (2000) 1213-1221
74. Dubray B., Breton C., Delic J., et al. In vitro radiation-induced apoptosis and early response to low-dose radiotherapy in non-Hodgkin's lymphomas. Radiother Oncol 46 (1998) 185-191
75. Szostak M.J., Kaur P., Amin P., et al. Apoptosis and bcl-2 expression in prostate cancer: significance in clinical outcome after brachytherapy. J Urol 165 (2001) 2126-2130
76. Bartelink H., Begg A., Martin J.C., et al. Towards prediction and modulation of treatment response. Radiother Oncol 50 (1999) 1-11
77. Corvo R., Antognoni P., and Sanguineti G. Biological predictors of response to radiotherapy in head and neck cancer: recent advances and emerging perspectives. Tumori 87 (2001) 355-363
78. Hofstra L., Liem I.H., Dumont E.A., et al. Visualisation of cell death in vivo in patients with acute myocardial infarction. Lancet 356 (2000) 209-212
79. Narula J., Acio E.R., Narula N., et al. Annexin-V imaging for noninvasive detection of cardiac allograft rejection. Nature Med 17 (2001) 1347-1352
80. Pierotti M.A., and Dragani T.A. Genetics and cancer. Curr Opin Oncol 4 (1992) 127-133
81. Von Pawel J. Gefitinib (Iressa, ZD1839): a novel targeted approach for the treatment of solid tumors. Bull Cancer 2004; 9:70-6.
82. Serganova I., and Blasberg R. Reporter gene imaging: potential impact on therapy. Nucl Med Biol 32 (2005) 763-780
83. Krozely P. Epidermal growth factor receptor tyrosine kinase inhibitors: evolving role in the treatment of solid tumors. Clin J Oncol Nurs 8 (2004) 163-168
84. Baumann M., and Krause M. Targeting the epidermal growth factor receptor in radiotherapy: radiobiological mechanisms, preclinical and clinical results. Radiother Oncol 72 (2004) 257-266
85. Ramos-Suzarte M., Rodriguez N., Oliva J.P., et al. 99mTc-labeled antihuman epidermal growth factor receptor antibody in patients with tumors of epithelial origin: part III. Clinical trials safety and diagnostic efficacy. J Nucl Med 40 (1999) 768-775
86. Adiedj A. Epidermal growth factor receptor tyrosine kinase inhibitors in cancer therapy. Drugs Future 26 (2001) 1087-1092
87. Haringhuizen A., van Tinteren H., Vaessen H.F., et al. Gefitinib as a last treatment option for non-small-cell lung cancer: durable disease control in a subset of patients. Ann Oncol 15 (2004) 786-792
88. Fukuoka M., Yano S., Giaccone G., et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. J Clin Oncol 21 (2003) 2237-2246
89. Sawyers C.L. Opportunities and challenges in the development of kinase inhibitor therapy for cancer. Genes Dev 17 (2003) 2998-3010
90. Elstrom R.L., Bauer D.E., Buzzai M., et al. AKT stimulates aerobic glycolysis in cancer cells. Cancer Res 64 (2004) 3892-3899
91. Van den Abbeele A.D., and Badawi R.D. Use of positron emission tomography in oncology and its potential role to assess response to Imatinib mesylate therapy in gastrointestinal stromal tumors (GISTs). Eur J Cancer 38 (2002) S60-S65
92. Antoch G., Kanja J., Bauer S., et al. Comparison of PET, CT, and dual-modality PET/CT imaging for monitoring of Imatinib (STI571) therapy in patients with gastrointestinal stromal tumors. J Nucl Med 45 (2004) 357-365
93. Demetri G.D., von Mehren M., Blanke C.D., et al. Efficacy and safety of Imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347 (2002) 472-480
94. 18FDG-positron emission tomography for the early prediction of response in advanced soft tissue sarcoma treated with Imatinib mesylate (Glivec). Eur J Cancer 39 (2003) 2012-2020
95. Zielhuis S.W., Nijsen J.F., Seppenwoolde J.H., et al. Lanthanide bearing microparticulate systems for multi-modality imaging and targeted therapy of cancer. Curr Med Chem Anticancer Agents 5 (2005) 303-313
96. He J., Liu G., Gupta S., et al. Amplification targeting: a modified pretargeting approach with potential for signal amplification-proof of a concept. J Nucl Med 45 (2004) 1087-1095
97. Dehdashti F., Mortimer J.E., Siegel B.A., et al. Positron tomography assessment of estrogen receptors in breast cancer: comparison with FDG PET and in vitro receptor assays. J Nucl Med 36 (1995) 1766-1774
98. 18F]fluoro-17-(-methyl-5(-dihydrotestosterone: a ligand for receptor mediated imaging of prostate cancer. Nucl Med Biol 28 (2001) 85-90
99. 64CU-TETA-Tyr-octreotate. A new somatostatine analogue with improved target tissue uptake. Nucl Med Biol 26 (1999) 267-273
100. Shulkin B.L., Wieland D.M., Schwaiger M., et al. PET scanning with hydroxyephedrine: an approach to the localisation of pheochromocytoma. J Nucl Med 33 (1992) 1125-1131
101. Bander N.H., Milowsky M.I., Nanus D.M., et al. Phase I trial of 177lutetium-labeled J591, a monoclonal antibody to prostate-specific membrane antigen, in patients with androgen-independent prostate cancer. J Clin Oncol 23 (2005) 4591-4601
102. Line B.R., Mitra A., Nan A., and Ghandehari H. Targeting tumor angiogenesis: comparison of peptide and polymer-peptide conjugates. J Nucl Med 46 (2005) 1552-1560
103. Ohira H., Kubota K., Ohuchi N., Harada Y., Fukuda H., and Satomi S. Comparison of intratumoral distribution of 99mTc-MIBI and deoxyglucose in mouse breast cancer models. J Nucl Med 41 (2000) 1561-1568
104. Rowell N.P., McCready V.R., Tait D., et al. Technetium-99m HMPAO and SPECT in the assessment of blood flow in human lung tumours. Br J Cancer 59 (1989) 135-141
105. Anderson H.L., Yap J.T., Miller M.P., Robbins A., Jones T., and Price P.M. Assessment of pharmacodynamic vascular response in a phase I trial of combretastatin A4 phosphate. J Clin Oncol 21 (2003) 2823-2830
106. Wang G., Dong Z., Xu G., Yang Z., et al. The effect of antibody against vascular endothelial growth factor on tumor growth and metastasis. J Cancer Res Clin Oncol 124 (1998) 615-620
107. Haubner R., Wester H.J., Reuning U., et al. Radiolabeled alpha(v)-beta3 integrin antagonists: a new class of tracers for tumor targeting. J Nucl Med 40 (1999) 1061-1071
108. Haubner R., Wester H.J., Weber W.A., et al. Noninvasive imaging of alpha(v)beta3 integrin expression using 18F-labeled RGD-containing glycopepetide and positron emission tomography. Cancer Res 61 (2001) 1781-1785
109. Hoffman R.M. In vivo cell biology of cancer cells visualized with fluorescent proteins. Curr Top Dev Biol 70 (2005) 121-144
110. Bekis R., Degirmenci B., Aydin A., et al. H. correlation between 99mTc-MIBI uptake and angiogenesis in MIBI-positive breast lesions. Nucl Med Biol 32 (2005) 465-472
111. Paik J.Y., Lee K.H., Ko B.H., et al. Nitric oxide stimulates 18F-FDG uptake in human endothelial cells through increased hexokinase activity and GLUT1 expression. J Nucl Med 46 (2005) 365-370