Abstract
Molecular imaging employing PET/CT enables in vivo visualization, characterization, and measurement of biologic processes in tumors at a molecular and cellular level. Using specific metabolic tracers, information about the integrated function of multiple transporters and enzymes involved in tumor metabolic pathways can be depicted, and the tracers can be directly applied as biomarkers of tumor biology. In this review, we discuss the role of F-18-fluorodeoxyglucose (FDG) as an in vivo glycolytic marker which reflects alterations of glucose metabolism in cancer cells. This functional molecular imaging technique offers a complementary approach to anatomic imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) and has found widespread application as a diagnostic modality in oncology to monitor tumor biology, optimize the therapeutic management, and guide patient care. Moreover, emerging methods for PET imaging of further biologic processes relevant to cancer are reviewed, with a focus on tumor hypoxia and aberrant tumor perfusion. Hypoxic tumors are associated with poor disease control and increased resistance to cytotoxic and radiation treatment. In vivo imaging of hypoxia, perfusion, and mismatch of metabolism and perfusion has the potential to identify specific features of tumor microenvironment associated with poor treatment outcome and, thus, contribute to personalized treatment approaches.
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References
Adams GE, Stratford IJ (1986) Hypoxia-mediated nitro-heterocyclic drugs in the radio- and chemotherapy of cancer. An overview. Biochem Pharmacol 35(1):71–76
Aerts HJ, Velazquez ER, Leijenaar RT, Parmar C, Grossmann P, Cavalho S, Bussink J, Monshouwer R, Haibe-Kains B, Rietveld D, Hoebers F, Rietbergen MM, Leemans CR, Dekker A, Quackenbush J, Gillies RJ, Lambin P (2014) Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach. Nat Commun 5:4006. doi:10.1038/ncomms5006
Allen-Auerbach M, Weber WA (2009) Measuring response with FDG-PET: methodological aspects. Oncologist 14(4):369–377. doi:10.1634/theoncologist.2008-0119
Alvarez JV, Belka GK, Pan TC, Chen CC, Blankemeyer E, Alavi A, Karp J, Chodosh LA (2014) Oncogene pathway activation in mammary tumors dictates [18F]-FDG-PET uptake. Cancer Res. doi:10.1158/0008-5472.CAN-14-1235
Apostolova I, Steffen IG, Wedel F, Lougovski A, Marnitz S, Derlin T, Amthauer H, Buchert R, Hofheinz F, Brenner W (2014a) Asphericity of pretherapeutic tumour FDG uptake provides independent prognostic value in head-and-neck cancer. Eur Radiol 24(9):2077–2087. doi:10.1007/s00330-014-3269-8
Apostolova I, Hofheinz F, Buchert R, Steffen IG, Michel R, Rosner C, Prasad V, Kohler C, Derlin T, Brenner W, Marnitz S (2014) Combined measurement of tumor perfusion and glucose metabolism for improved tumor characterization in advanced cervical carcinoma. A PET/CT pilot study using [15O]water and [18F]fluorodeoxyglucose. Strahlentherapie und Onkologie: Organ der Deutschen Rontgengesellschaft [et al] 190(6):575–581. doi:10.1007/s00066-014-0611-7
Arabi M, Piert M (2010) Hypoxia PET/CT imaging: implications for radiation oncology. Q J Nucl Med Mol Imaging Off Publ Ital Assoc Nucl Med 54(5):500–509
Bahri H, Laurence L, Edeline J, Leghzali H, Devillers A, Raoul JL, Cuggia M, Mesbah H, Clement B, Boucher E, Garin E (2014) High prognostic value of 18F-FDG PET for metastatic gastroenteropancreatic neuroendocrine tumors: a long-term evaluation. J Nucl Med Off Publ Soc Nucl Med. doi:10.2967/jnumed.114.144386
Bensinger SJ, Christofk HR (2012) New aspects of the Warburg effect in cancer cell biology. Semin Cell Dev Biol 23(4):352–361. doi:10.1016/j.semcdb.2012.02.003
Bland JM, Altman DG (1999) Measuring agreement in method comparison studies. Stat Methods Med Res 8(2):135–160
Bourgeois M, Rajerison H, Guerard F, Mougin-Degraef M, Barbet J, Michel N, Cherel M, Faivre-Chauvet A (2011) Contribution of [64Cu]-ATSM PET in molecular imaging of tumour hypoxia compared to classical [18F]-MISO–a selected review. Nucl Med Rev Central East Eur 14(2):90–95
Bradley J, Thorstad WL, Mutic S, Miller TR, Dehdashti F, Siegel BA, Bosch W, Bertrand RJ (2004) Impact of FDG-PET on radiation therapy volume delineation in non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 59(1):78–86. doi:10.1016/j.ijrobp.2003.10.044
Brenner W, Conrad EU, Eary JF (2004) FDG PET imaging for grading and prediction of outcome in chondrosarcoma patients. Eur J Nucl Med Mol Imaging 31:189–195
Brenner W, Friedrich RE, Gawad KA, Hagel C, von Deimling A., de Wit M, Buchert R, Clausen M, Mautner VF (2006a) Prognostic relevance of FDG PET in patients with neurofibromatosis type-1 and malignant peripheral nerve sheath tumors. Eur J Nucl Med Mol Imaging 33:428–432
Brenner W, Hwang W, Vernon C, Conrad EU, Eary JF (2006b) Risk assessment in liposarcoma patients based on FDG-PET imaging. Eur J Nucl Med Mol Imaging 33:1290–1295
Brizel DM, Scully SP, Harrelson JM, Layfield LJ, Bean JM, Prosnitz LR, Dewhirst MW (1996) Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer Res 56(5):941–943
Buck AK, Halter G, Schirrmeister H, Kotzerke J, Wurziger I, Glatting G, Mattfeldt T, Neumaier B, Reske SN, Hetzel M (2003) Imaging proliferation in lung tumors with PET: 18F-FLT versus 18F-FDG. J Nucl Med Off Publ Soc Nucl Med 44(9):1426–1431
Buerkle A, Weber WA (2008) Imaging of tumor glucose utilization with positron emission tomography. Cancer Metastasis Rev 27(4):545–554. doi:10.1007/s10555-008-9151-x
Bui T, Thompson CB (2006) Cancer’s sweet tooth. Cancer cell 9(6):419–420. doi:10.1016/j.ccr.2006.05.012
Busk M, Horsman MR, Jakobsen S, Bussink J, van der Kogel A, Overgaard J (2008a) Cellular uptake of PET tracers of glucose metabolism and hypoxia and their linkage. Eur J Nucl Med Mol Imaging 35(12):2294–2303. doi:10.1007/s00259-008-0888-9
Busk M, Horsman MR, Jakobsen S, Keiding S, van der Kogel AJ, Bussink J, Overgaard J (2008b) Imaging hypoxia in xenografted and murine tumors with 18F-fluoroazomycin arabinoside: a comparative study involving microPET, autoradiography, PO2-polarography, and fluorescence microscopy. Int J Radiat Oncol Biol Phys 70(4):1202–1212. doi:10.1016/j.ijrobp.2007.11.034
Caetano R, Bastos CR, de Oliveira IA, da Silva RM, Fortes CP, Pepe VL, Reis LG, Braga JU (2014) Accuracy of PET and PET-CT in the detection of differentiated thyroid cancer recurrence with negative I whole body scan results: a meta-analysis. Head Neck. doi:10.1002/hed.23881
Cheng J, Lei L, Xu J, Sun Y, Zhang Y, Wang X, Pan L, Shao Z, Zhang Y, Liu G (2013) 18F-fluoromisonidazole PET/CT: a potential tool for predicting primary endocrine therapy resistance in breast cancer. J Nucl Med Off Publ Soc Nucl Med 54(3):333–340. doi:10.2967/jnumed.112.111963
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA (2014) Recommendations for initial evaluation, staging, and response assessment of hodgkin and non-hodgkin lymphoma: the lugano classification. J Clin Oncol Off J Am Soc Clin Oncol. doi:10.1200/JCO.2013.54.8800
Chicklore S, Goh V, Siddique M, Roy A, Marsden PK, Cook GJ (2013) Quantifying tumour heterogeneity in 18F-FDG PET/CT imaging by texture analysis. Eur J Nucl Med Mol Imaging 40(1):133–140. doi:10.1007/s00259-012-2247-0
Cook GJ, Yip C, Siddique M, Goh V, Chicklore S, Roy A, Marsden P, Ahmad S, Landau D (2013) Are pretreatment 18F-FDG PET tumor textural features in non-small cell lung cancer associated with response and survival after chemoradiotherapy? J Nucl Med Off Publ Soc Nucl Med 54(1):19–26. doi:10.2967/jnumed.112.107375
de Langen AJ, van den Boogaart VE, Marcus JT, Lubberink M (2008) Use of H2(15)O-PET and DCE-MRI to measure tumor blood flow. Oncologist 13(6):631–644. doi:10.1634/theoncologist.2007-0235
Dewan NA, Reeb SD, Gupta NC, Gobar LS, Scott WJ (1995) PET-FDG imaging and transthoracic needle lung aspiration biopsy in evaluation of pulmonary lesions. A comparative risk-benefit analysis. Chest 108(2):441–446
Di Chiro G, Bairamian D (1988) Brain imaging of glucose utilization in cerebral tumors. Am J Physiol Imaging 3(1):56
Di Chiro G, DeLaPaz RL, Brooks RA, Sokoloff L, Kornblith PL, Smith BH, Patronas NJ, Kufta CV, Kessler RM, Johnston GS, Manning RG, Wolf AP (1982) Glucose utilization of cerebral gliomas measured by [18F] fluorodeoxyglucose and positron emission tomography. Neurology 32(12):1323–1329
Duan XY, Wang W, Wang JS, Shang J, Gao JG, Guo YM (2013) Fluorodeoxyglucose positron emission tomography and chemotherapy-related tumor marker expression in non-small cell lung cancer. BMC Cancer 13:546. doi:10.1186/1471-2407-13-546
Dunnwald LK, Gralow JR, Ellis GK, Livingston RB, Linden HM, Specht JM, Doot RK, Lawton TJ, Barlow WE, Kurland BF, Schubert EK, Mankoff DA (2008) Tumor metabolism and blood flow changes by positron emission tomography: relation to survival in patients treated with neoadjuvant chemotherapy for locally advanced breast cancer. J Clin Oncol Off J Am Soc Clin Oncol 26(27):4449–4457. doi:10.1200/JCO.2007.15.4385
Eary JF, O’Sullivan F, O’Sullivan J, Conrad EU (2008) Spatial heterogeneity in sarcoma 18F-FDG uptake as a predictor of patient outcome. J Nucl Med Off Publ Soc Nucl Med 49(12):1973–1979. doi:10.2967/jnumed.108.053397
Ekmekcioglu O, Aliyev A, Yilmaz S, Arslan E, Kaya R, Kocael P, Erkan ME, Halac M, Sonmezoglu K (2013) Correlation of 18F-fluorodeoxyglucose uptake with histopathological prognostic factors in breast carcinoma. Nucl Med Commun 34(11):1055–1067. doi:10.1097/MNM.0b013e3283658369
El Naqa I, Grigsby P, Apte A, Kidd E, Donnelly E, Khullar D, Chaudhari S, Yang D, Schmitt M, Laforest R, Thorstad W, Deasy JO (2009) Exploring feature-based approaches in PET images for predicting cancer treatment outcomes. Pattern Recogn 42(6):1162–1171. doi:10.1016/j.patcog.2008.08.011
Eschmann SM, Friedel G, Paulsen F, Reimold M, Hehr T, Budach W, Langen HJ, Bares R (2007) 18F-FDG PET for assessment of therapy response and preoperative re-evaluation after neoadjuvant radio-chemotherapy in stage III non-small cell lung cancer. Eur J Nucl Med Mol Imaging 34(4):463–471. doi:10.1007/s00259-006-0273-5
Ferrer Albiach C, Conde Moreno A, Rodriguez Cordon M, Morillo Macias V, Bouche Babiloni A, Beato Tortajada I, Sanchez Iglesias A, Frances Munoz A (2010) Contribution of hypoxia-measuring molecular imaging techniques to radiotherapy planning and treatment. Clin Transl Oncol Off Publ Fed Span Oncol Soc Nat Cancer Inst Mex 12(1):22–26. doi:10.1007/s12094-010-0462-3
Folpe AL, Lyles RH, Sprouse JT, Conrad EU 3rd, Eary JF (2000) (F-18) fluorodeoxyglucose positron emission tomography as a predictor of pathologic grade and other prognostic variables in bone and soft tissue sarcoma. Clin Cancer Res Off J Am Assoc Cancer Res 6(4):1279–1287
Furth C, Steffen IG, Amthauer H, Ruf J, Misch D, Schonberger S, Kobe C, Denecke T, Stover B, Hautzel H, Henze G, Hundsdoerfer P (2009) Early and late therapy response assessment with [18F]fluorodeoxyglucose positron emission tomography in pediatric Hodgkin’s lymphoma: analysis of a prospective multicenter trial. J Clin Oncol Off J Am Soc Clin Oncol 27(26):4385–4391. doi:10.1200/JCO.2008.19.7814
Gagel B, Reinartz P, Dimartino E, Zimny M, Pinkawa M, Maneschi P, Stanzel S, Hamacher K, Coenen HH, Westhofen M, Bull U, Eble MJ (2004) pO(2) Polarography versus positron emission tomography ([(18)F] fluoromisonidazole, [(18)F]-2-fluoro-2′-deoxyglucose). An appraisal of radiotherapeutically relevant hypoxia. Strahlentherapie und Onkologie: Organ der Deutschen Rontgengesellschaft [et al] 180(10):616–622. doi:10.1007/s00066-004-1229-y
Gagel B, Reinartz P, Demirel C, Kaiser HJ, Zimny M, Piroth M, Pinkawa M, Stanzel S, Asadpour B, Hamacher K, Coenen HH, Buell U, Eble MJ (2006) [18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography in response evaluation after chemo-/radiotherapy of non-small-cell lung cancer: a feasibility study. BMC Cancer 6:51. doi:10.1186/1471-2407-6-51
Gallamini A, Barrington SF, Biggi A, Chauvie S, Kostakoglu L, Gregianin M, Meignan M, Mikhaeel GN, Loft A, Zaucha JM, Seymour JF, Hofman MS, Rigacci L, Pulsoni A, Coleman M, Dann EJ, Trentin L, Casasnovas O, Rusconi C, Brice P, Bolis S, Viviani S, Salvi F, Luminari S, Hutchings M (2014) The predictive role of interim positron emission tomography for Hodgkin lymphoma treatment outcome is confirmed using the interpretation criteria of the Deauville five-point scale. Haematologica 99(6):1107–1113. doi:10.3324/haematol.2013.103218
Garcia Garcia-Esquinas M, Garcia-Saenz JA, Arrazola Garcia J, Enrique Fuentes Ferrer M, Furio V, Rodriguez Rey C, Roman JM, Carreras Delgado JL (2014) 18F-FDG PET-CT imaging in the neoadjuvant setting for stages II–III breast cancer: association of locoregional SUVmax with classical prognostic factors. Q J Nucl Med Mol Imaging Off Publ Ital Assoc Nucl Med 58(1):66–73
Garcia-Parra R, Wood D, Shah RB, Siddiqui J, Hussain H, Park H, Desmond T, Meyer C, Piert M (2011) Investigation on tumor hypoxia in resectable primary prostate cancer as demonstrated by 18F-FAZA PET/CT utilizing multimodality fusion techniques. Eur J Nucl Med Mol Imaging 38(10):1816–1823. doi:10.1007/s00259-011-1876-z
Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK (2001) Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA 285(7):914–924
Gould MK, Sanders GD, Barnett PG, Rydzak CE, Maclean CC, McClellan MB, Owens DK (2003) Cost-effectiveness of alternative management strategies for patients with solitary pulmonary nodules. Ann Intern Med 138(9):724–735
Gupta NC, Frank AR, Dewan NA, Redepenning LS, Rothberg ML, Mailliard JA, Phalen JJ, Sunderland JJ, Frick MP (1992) Solitary pulmonary nodules: detection of malignancy with PET with 2-[F-18]-fluoro-2-deoxy-D-glucose. Radiology 184(2):441–444. doi:10.1148/radiology.184.2.1620844
Hamilton G, Rath B (2014) A short update on cancer chemoresistance. Wien Med Wochenschr. doi:10.1007/s10354-014-0311-z
Han MW, Lee HJ, Cho KJ, Kim JS, Roh JL, Choi SH, Nam SY, Kim SY (2012) Role of FDG-PET as a biological marker for predicting the hypoxic status of tongue cancer. Head Neck 34(10):1395–1402. doi:10.1002/hed.21945
Hayashi K, Furutsuka K, Takei M, Muto M, Nakao R, Aki H, Suzuki K, Fukumura T (2011) High-yield automated synthesis of [18F]fluoroazomycin arabinoside ([18F]FAZA) for hypoxia-specific tumor imaging. Appl Rad Isot Incl Data Instrum Methods Use Agric Ind Med 69(7):1007–1013. doi:10.1016/j.apradiso.2011.02.025
Hockel M, Vaupel P (2001) Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst 93(4):266–276
Holdsworth CH, Badawi RD, Manola JB, Kijewski MF, Israel DA, Demetri GD, Van den Abbeele AD (2007) CT and PET: early prognostic indicators of response to imatinib mesylate in patients with gastrointestinal stromal tumor. AJR Am J Roentgenol 189(6):W324–W330. doi:10.2214/AJR.07.2496
Hutchings M, Loft A, Hansen M, Pedersen LM, Buhl T, Jurlander J, Buus S, Keiding S, D’Amore F, Boesen AM, Berthelsen AK, Specht L (2006) FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. Blood 107(1):52–59. doi:10.1182/blood-2005-06-2252
Hutchings M, Kostakoglu L, Zaucha JM, Malkowski B, Biggi A, Danielewicz I, Loft A, Specht L, Lamonica D, Czuczman MS, Nanni C, Zinzani PL, Diehl L, Stern R, Coleman M (2014) In vivo treatment sensitivity testing with positron emission tomography/computed tomography after one cycle of chemotherapy for Hodgkin lymphoma. J Clin Oncol Off J Am Soc Clin Oncol 32(25):2705–2711. doi:10.1200/JCO.2013.53.2838
Izuishi K, Yamamoto Y, Mori H, Kameyama R, Fujihara S, Masaki T, Suzuki Y (2014) Molecular mechanisms of [18F]fluorodeoxyglucose accumulation in liver cancer. Oncol Rep 31(2):701–706. doi:10.3892/or.2013.2886
Jacobson O, Chen X (2013) Interrogating tumor metabolism and tumor microenvironments using molecular positron emission tomography imaging. Theranostic approaches to improve therapeutics. Pharmacol Rev 65(4):1214–1256. doi:10.1124/pr.113.007625
Jerabek PA, Patrick TB, Kilbourn MR, Dischino DD, Welch MJ (1986) Synthesis and biodistribution of 18F-labeled fluoronitroimidazoles: potential in vivo markers of hypoxic tissue. Int J Radiat Appl Instrum Part A Appl Rad Isot 37(7):599–605
Kaira K, Oriuchi N, Sunaga N, Ishizuka T, Shimizu K, Yamamoto N (2011) A systemic review of PET and biology in lung cancer. Am J Transl Res 3(4):383–391
Kalff VV, Hicks R, Ware R, Binns D, McKenzie A (2000) 29. F-18 FDG PET for suspected or confirmed regional recurrence of colon cancer. A prospective study of impact and outcome. Clin Positron Imaging Off J Inst Clin PET 3 4:183
Keith CJ, Miles KA, Griffiths MR, Wong D, Pitman AG, Hicks RJ (2002) Solitary pulmonary nodules: accuracy and cost-effectiveness of sodium iodide FDG-PET using Australian data. Eur J Nucl Med Mol Imaging 29(8):1016–1023. doi:10.1007/s00259-002-0833-2
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) Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clin Cancer Res Off J Am Assoc Cancer Res 11(8):2785–2808. doi:10.1158/1078-0432.CCR-04-2626
Khan MA, Combs CS, Brunt EM, Lowe VJ, Wolverson MK, Solomon H, Collins BT, Di Bisceglie AM (2000) Positron emission tomography scanning in the evaluation of hepatocellular carcinoma. J Hepatol 32(5):792–797
Kim JW, Dang CV (2006) Cancer’s molecular sweet tooth and the Warburg effect. Cancer Res 66(18):8927–8930. doi:10.1158/0008-5472.CAN-06-1501
Koh WJ, Rasey JS, Evans ML, Grierson JR, Lewellen TK, Graham MM, Krohn KA, Griffin TW (1992) Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole. Int J Radiat Oncol Biol Phys 22(1):199–212
Komar G, Kauhanen S, Liukko K, Seppanen M, Kajander S, Ovaska J, Nuutila P, Minn H (2009) Decreased blood flow with increased metabolic activity: a novel sign of pancreatic tumor aggressiveness. Clin Cancer Res Off J Am Assoc Cancer Res 15(17):5511–5517. doi:10.1158/1078-0432.CCR-09-0414
Kostakoglu L, Gallamini A (2013) Interim 18F-FDG PET in Hodgkin lymphoma: would PET-adapted clinical trials lead to a paradigm shift? J Nucl Med Off Publ Soc Nucl Med 54(7):1082–1093. doi:10.2967/jnumed.113.120451
Krause BJ, Beck R, Souvatzoglou M, Piert M (2006) PET and PET/CT studies of tumor tissue oxygenation. Q J Nucl Med Mol Imaging Off Publ Ital Assoc Nucl Med 50(1):28–43
Krohn KA, Mankoff DA, Muzi M, Link JM, Spence AM (2005) True tracers: comparing FDG with glucose and FLT with thymidine. Nucl Med Biol 32(7):663–671. doi:10.1016/j.nucmedbio.2005.04.004
Kumar P, Stypinski D, **a H, McEwan AJB, Machulla H-J, Wiebe LI (1999) Fluoroazomycin arabinoside (FAZA): synthesis, 2H and 3H-labelling and preliminary biological evaluation of a novel 2-nitroimidazole marker of tissue hypoxia. J Label Compd Radiopharm 42(1):3–16
Lambin P, Rios-Velazquez E, Leijenaar R, Carvalho S, van Stiphout RG, Granton P, Zegers CM, Gillies R, Boellard R, Dekker A, Aerts HJ (2012) Radiomics: extracting more information from medical images using advanced feature analysis. Eur J Cancer 48(4):441–446. doi:10.1016/j.ejca.2011.11.036
Lapi SE, Voller TF, Welch MJ (2009) Positron emission tomography imaging of hypoxia. PET Clin 4(1):39–47. doi:10.1016/j.cpet.2009.05.009
Lawrentschuk N, Poon AM, Foo SS, Putra LG, Murone C, Davis ID, Bolton DM, Scott AM (2005) Assessing regional hypoxia in human renal tumours using 18F-fluoromisonidazole positron emission tomography. BJU Int 96(4):540–546. doi:10.1111/j.1464-410X.2005.05681.x
Lee NY, Mechalakos JG, Nehmeh S, Lin Z, Squire OD, Cai S, Chan K, Zanzonico PB, Greco C, Ling CC, Humm JL, Schoder H (2008) Fluorine-18-labeled fluoromisonidazole positron emission and computed tomography-guided intensity-modulated radiotherapy for head and neck cancer: a feasibility study. Int J Radiat Oncol Biol Phys 70(1):2–13. doi:10.1016/j.ijrobp.2007.06.039
Leong T, Everitt C, Yuen K, Condron S, Hui A, Ngan SY, Pitman A, Lau EW, MacManus M, Binns D, Ackerly T, Hicks RJ (2006) A prospective study to evaluate the impact of FDG-PET on CT-based radiotherapy treatment planning for oesophageal cancer. Radiother Oncol J Eur Soc Ther Radiol Oncol 78(3):254–261. doi:10.1016/j.radonc.2006.02.014
Lim JL, Berridge MS (1993) An efficient radiosynthesis of [18F]fluoromisonidazole. Appl Radiat Isot Incl Data Instrum Methods Use Agric Ind Med 44(8):1085–1091
Lodge MA, Jacene HA, Pili R, Wahl RL (2008) Reproducibility of tumor blood flow quantification with 15O-water PET. J Nucl Med Off Publ Soc Nucl Med 49(10):1620–1627. doi:10.2967/jnumed.108.052076
Macapinlac HA (2004) FDG PET and PET/CT imaging in lymphoma and melanoma. Cancer J 10(4):262–270
Mah K, Caldwell CB, Ung YC, Danjoux CE, Balogh JM, Ganguli SN, Ehrlich LE, Tirona R (2002) The impact of (18)FDG-PET on target and critical organs in CT-based treatment planning of patients with poorly defined non-small-cell lung carcinoma: a prospective study. Int J Radiat Oncol Biol Phys 52(2):339–350
Mankoff DA, Dunnwald LK, Partridge SC, Specht JM (2009) Blood flow-metabolism mismatch: good for the tumor, bad for the patient. Clin Cancer Res Off J Am Assoc Cancer Res 15(17):5294–5296. doi:10.1158/1078-0432.CCR-09-1448
Mano Y, Aishima S, Kubo Y, Tanaka Y, Motomura T, Toshima T, Shirabe K, Baba S, Maehara Y, Oda Y (2014) Correlation between biological marker expression and fluorine-18 fluorodeoxyglucose uptake in hepatocellular carcinoma. Am J Clin Pathol 142(3):391–397. doi:10.1309/AJCPG8AFJ5NRKLLM
Mathupala SP, Rempel A, Pedersen PL (1997) Aberrant glycolytic metabolism of cancer cells: a remarkable coordination of genetic, transcriptional, post-translational, and mutational events that lead to a critical role for type II hexokinase. J Bioenerg Biomembr 29(4):339–343
Mawlawi O, Townsend DW (2009) Multimodality imaging: an update on PET/CT technology. Eur J Nucl Med Mol Imaging 36(Suppl 1):S15–S29. doi:10.1007/s00259-008-1016-6
Mees G, Dierckx R, Vangestel C, Laukens D, Van Damme N, Van de Wiele C (2013) Pharmacologic activation of tumor hypoxia: a means to increase tumor 2-deoxy-2-[18F]fluoro-D-glucose uptake? Mol Imaging 12(1):49–58
Minn H, Zasadny KR, Quint LE, Wahl RL (1995) Lung cancer: reproducibility of quantitative measurements for evaluating 2-[F-18]-fluoro-2-deoxy-D-glucose uptake at PET. Radiology 196(1):167–173. doi:10.1148/radiology.196.1.7784562
Mortensen LS, Johansen J, Kallehauge J, Primdahl H, Busk M, Lassen P, Alsner J, Sorensen BS, Toustrup K, Jakobsen S, Petersen J, Petersen H, Theil J, Nordsmark M, Overgaard J (2012) FAZA PET/CT hypoxia imaging in patients with squamous cell carcinoma of the head and neck treated with radiotherapy: results from the DAHANCA 24 trial. Radiother Oncol J Eur Soc Ther Radiol Oncol 105(1):14–20. doi:10.1016/j.radonc.2012.09.015
Oda Y, Kondo M (1994) Noninvasive quantitative evaluation of regional myocardial blood flow and tissue fraction with O-15-labeled water and carbon dioxide inhalation using dynamic positron emission tomography. Nihon rinsho Japan J Clin Med 52 Suppl (Pt 1):614–621
Okamoto S, Shiga T, Yasuda K, Ito YM, Magota K, Kasai K, Kuge Y, Shirato H, Tamaki N (2013) High reproducibility of tumor hypoxia evaluated by 18F-fluoromisonidazole PET for head and neck cancer. J Nucl Med Off Publ Soc Nucl Med 54(2):201–207. doi:10.2967/jnumed.112.109330
Padhani AR (2005) Where are we with imaging oxygenation in human tumours? Cancer Imaging Off Publ Int Cancer Imaging Soc 5:128–130. doi:10.1102/1470-7330.2005.0103
Patronas NJ, Di Chiro G, Kufta C, Bairamian D, Kornblith PL, Simon R, Larson SM (1985) Prediction of survival in glioma patients by means of positron emission tomography. J Neurosurg 62(6):816–822. doi:10.3171/jns.1985.62.6.0816
Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE (1979) Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method. Ann Neurol 6(5):371–388. doi:10.1002/ana.410060502
Piert M, Machulla HJ, Picchio M, Reischl G, Ziegler S, Kumar P, Wester HJ, Beck R, McEwan AJ, Wiebe LI, Schwaiger M (2005) Hypoxia-specific tumor imaging with 18F-fluoroazomycin arabinoside. J Nucl Med Off Publ Soc Nucl Med 46(1):106–113
Plathow C, Weber WA (2008) Tumor cell metabolism imaging. J Nucl Med Off Publ Soc Nucl Med 49(Suppl 2):43S–63S. doi:10.2967/jnumed.107.045930
Rahmim A, Zaidi H (2008) PET versus SPECT: strengths, limitations and challenges. Nucl Med Commun 29(3):193–207. doi:10.1097/MNM.0b013e3282f3a515
Rajendran JG, Schwartz DL, O’Sullivan J, Peterson LM, Ng P, Scharnhorst J, Grierson JR, Krohn KA (2006) Tumor hypoxia imaging with [F-18] fluoromisonidazole positron emission tomography in head and neck cancer. Clin Cancer Res Off J Am Assoc Cancer Res 12(18):5435–5441. doi:10.1158/1078-0432.CCR-05-1773
Reischl G, Ehrlichmann W, Bieg C, Solbach C, Kumar P, Wiebe LI, Machulla HJ (2005) Preparation of the hypoxia imaging PET tracer [18F]FAZA: reaction parameters and automation. Appl Radiat Isot Incl Data Instrum Methods Use Agric Ind Med 62(6):897–901. doi:10.1016/j.apradiso.2004.12.004
Reivich M, Kuhl D, Wolf A, Greenberg J, Phelps M, Ido T, Casella V, Fowler J, Gallagher B, Hoffman E, Alavi A, Sokoloff L (1977) Measurement of local cerebral glucose metabolism in man with 18F-2-fluoro-2-deoxy-d-glucose. Acta Neurol Scand Suppl 64:190–191
Reivich M, Kuhl D, Wolf A, Greenberg J, Phelps M, Ido T, Casella V, Fowler J, Hoffman E, Alavi A, Som P, Sokoloff L (1979) The [18F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man. Circ Res 44(1):127–137
Sato J, Kitagawa Y, Yamazaki Y, Hata H, Okamoto S, Shiga T, Shindoh M, Kuge Y, Tamaki N (2013) 18F-fluoromisonidazole PET uptake is correlated with hypoxia-inducible factor-1alpha expression in oral squamous cell carcinoma. J Nucl Med Off Publ Soc Nucl Med 54(7):1060–1065. doi:10.2967/jnumed.112.114355
Semenza GL (2003) Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3(10):721–732. doi:10.1038/nrc1187
Semenza GL (2007) Hypoxia-inducible factor 1 (HIF-1) pathway. Science’s STKE: signal transduction knowledge environment 2007 (407):cm8. doi:10.1126/stke.4072007cm8
Semenza GL (2013) HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. J Clin Invest 123(9):3664–3671. doi:10.1172/JCI67230
Servagi-Vernat S, Differding S, Hanin FX, Labar D, Bol A, Lee JA, Gregoire V (2014) A prospective clinical study of (1)(8)F-FAZA PET-CT hypoxia imaging in head and neck squamous cell carcinoma before and during radiation therapy. Eur J Nucl Med Mol Imaging 41(8):1544–1552. doi:10.1007/s00259-014-2730-x
Shammas A, Degirmenci B, Mountz JM, McCook BM, Branstetter B, Bencherif B, Joyce JM, Carty SE, Kuffner HA, Avril N (2007) 18F-FDG PET/CT in patients with suspected recurrent or metastatic well-differentiated thyroid cancer. J Nucl Med Off Publ Soc Nucl Med 48(2):221–226
Simsek DH, Kuyumcu S, Turkmen C, Sanli Y, Aykan F, Unal S, Adalet I (2014) Can complementary 68 Ga-DOTATATE and 18F-FDG PET/CT establish the missing link between histopathology and therapeutic approach in gastroenteropancreatic neuroendocrine tumors? J Nucl Med Off Publ Soc Nucl Med. doi:10.2967/jnumed.114.142224
Sokoloff L (1977) Relation between physiological function and energy metabolism in the central nervous system. J Neurochem 29(1):13–26
Specht L (2007) 2-[18F]fluoro-2-deoxyglucose positron-emission tomography in staging, response evaluation, and treatment planning of lymphomas. Semin Radiat Oncol 17(3):190–197. doi:10.1016/j.semradonc.2007.02.005
Spence AM, Muzi M, Swanson KR, O’Sullivan F, Rockhill JK, Rajendran JG, Adamsen TC, Link JM, Swanson PE, Yagle KJ, Rostomily RC, Silbergeld DL, Krohn KA (2008) Regional hypoxia in glioblastoma multiforme quantified with [18F]fluoromisonidazole positron emission tomography before radiotherapy: correlation with time to progression and survival. Clin Cancer Res Off J Am Assoc Cancer Res 14(9):2623–2630. doi:10.1158/1078-0432.CCR-07-4995
Stone HB, Brown JM, Phillips TL, Sutherland RM (1993) Oxygen in human tumors: correlations between methods of measurement and response to therapy. Summary of a workshop held 19–20 Nov 1992, at the National Cancer Institute, Bethesda, Maryland. Radiation Res 136(3):422–434
Szablewski L (2013) Expression of glucose transporters in cancers. Biochim Biophys Acta 1835(2):164–169. doi:10.1016/j.bbcan.2012.12.004
Takebayashi R, Izuishi K, Yamamoto Y, Kameyama R, Mori H, Masaki T, Suzuki Y (2013) [18F]Fluorodeoxyglucose accumulation as a biological marker of hypoxic status but not glucose transport ability in gastric cancer. J Exp Clin Cancer Res CR 32:34. doi:10.1186/1756-9966-32-34
Tatum JL, Kelloff GJ, Gillies RJ, Arbeit JM, Brown JM, Chao KS, Chapman JD, Eckelman WC, Fyles AW, Giaccia AJ, Hill RP, Koch CJ, Krishna MC, Krohn KA, Lewis JS, Mason RP, Melillo G, Padhani AR, Powis G, Rajendran JG, Reba R, Robinson SP, Semenza GL, Swartz HM, Vaupel P, Yang D, Croft B, Hoffman J, Liu G, Stone H, Sullivan D (2006) Hypoxia: importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy. Int J Radiat Biol 82(10):699–757. doi:10.1080/09553000601002324
Taus A, Aguilo R, Curull V, Suarez-Pinera M, Rodriguez-Fuster A, Rodriguez de Dios N, Pijuan L, Zuccarino F, Vollmer I, Sanchez-Font A, Belda-Sanchis J, Arriola E (2014) Impact of 18F-FDG PET/CT in the treatment of patients with non-small cell lung cancer. Arch Bronconeumol 50(3):99–104. doi:10.1016/j.arbres.2013.09.017
Ter-Pogossian MM, Herscovitch P (1985) Radioactive oxygen-15 in the study of cerebral blood flow, blood volume, and oxygen metabolism. Semin Nucl Med 15(4):377–394
Tixier F, Le Rest CC, Hatt M, Albarghach N, Pradier O, Metges JP, Corcos L, Visvikis D (2011) Intratumor heterogeneity characterized by textural features on baseline 18F-FDG PET images predicts response to concomitant radiochemotherapy in esophageal cancer. J Nucl Med Off Publ Soc Nucl Med 52(3):369–378. doi:10.2967/jnumed.110.082404
Tixier F, Hatt M, Le Rest CC, Le Pogam A, Corcos L, Visvikis D (2012) Reproducibility of tumor uptake heterogeneity characterization through textural feature analysis in 18F-FDG PET. J Nucl Med Off Publ Soc Nucl Med 53(5):693–700. doi:10.2967/jnumed.111.099127
Tixier F, Hatt M, Valla C, Fleury V, Lamour C, Ezzouhri S, Ingrand P, Perdrisot R, Visvikis D, Cheze Le Rest C (2014) Visual versus quantitative assessment of intratumor 18F-FDG PET uptake heterogeneity: prognostic value in non-small cell lung cancer. J Nucl Med Off Publ Soc Nucl Med. doi:10.2967/jnumed.113.133389
Treglia G, Mirk P, Stefanelli A, Rufini V, Giordano A, Bonomo L (2012) 18F-Fluorodeoxyglucose positron emission tomography in evaluating treatment response to imatinib or other drugs in gastrointestinal stromal tumors: a systematic review. Clin Imaging 36(3):167–175. doi:10.1016/j.clinimag.2011.08.012
Trinkaus ME, Blum R, Rischin D, Callahan J, Bressel M, Segard T, Roselt P, Eu P, Binns D, MacManus MP, Ball D, Hicks RJ (2013) Imaging of hypoxia with 18F-FAZA PET in patients with locally advanced non-small cell lung cancer treated with definitive chemoradiotherapy. J Med Imaging Radiat Oncol 57(4):475–481. doi:10.1111/1754-9485.12086
Tseng J, Dunnwald LK, Schubert EK, Link JM, Minoshima S, Muzi M, Mankoff DA (2004) 18F-FDG kinetics in locally advanced breast cancer: correlation with tumor blood flow and changes in response to neoadjuvant chemotherapy. J Nucl Med Off Publ Soc Nucl Med 45(11):1829–1837
Ul-Hassan F, Simo R, Guerrero-Urbano T, Oakley R, Jeannon JP, Cook GJ (2013) Can (18)F-FDG PET/CT reliably assess response to primary treatment of head and neck cancer? Clin Nucl Med 38(4):263–265. doi:10.1097/RLU.0b013e31828165a8
Upadhyay M, Samal J, Kandpal M, Singh OV, Vivekanandan P (2013) The Warburg effect: insights from the past decade. Pharmacol Ther 137(3):318–330. doi:10.1016/j.pharmthera.2012.11.003
Vansteenkiste JF (2003) PET scan in the staging of non-small cell lung cancer. Lung Cancer 42(Suppl 1):S27–S37
Vanuytsel LJ, Vansteenkiste JF, Stroobants SG, De Leyn PR, De Wever W, Verbeken EK, Gatti GG, Huyskens DP, Kutcher GJ (2000) The impact of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) lymph node staging on the radiation treatment volumes in patients with non-small cell lung cancer. Radiother Oncol J Eur Soc Ther Radiol Oncol 55(3):317–324
Vaupel P, Mayer A (2007) Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev 26(2):225–239. doi:10.1007/s10555-007-9055-1
Vaupel P, Kallinowski F, Okunieff P (1989) Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res 49(23):6449–6465
Wadsak W, Mitterhauser M (2010) Basics and principles of radiopharmaceuticals for PET/CT. Eur J Radiol 73(3):461–469. doi:10.1016/j.ejrad.2009.12.022
Wang W, Lee NY, Georgi JC, Narayanan M, Guillem J, Schoder H, Humm JL (2010) Pharmacokinetic analysis of hypoxia (18)F-fluoromisonidazole dynamic PET in head and neck cancer. J Nucl Med Off Publ Soc Nucl Med 51(1):37–45. doi:10.2967/jnumed.109.067009
Warburg O, Wind F, Negelein E (1927) The metabolism of tumors in the body. J Gen Physiol 8(6):519–530
Weber WA, Wieder H (2006) Monitoring chemotherapy and radiotherapy of solid tumors. Eur J Nucl Med Mol Imaging 33(Suppl 1):27–37. doi:10.1007/s00259-006-0133-3
Weber WA, Schwaiger M, Avril N (2000) Quantitative assessment of tumor metabolism using FDG-PET imaging. Nucl Med Biol 27(7):683–687
Weber WA, Petersen V, Schmidt B, Tyndale-Hines L, Link T, Peschel C, Schwaiger M (2003) Positron emission tomography in non-small-cell lung cancer: prediction of response to chemotherapy by quantitative assessment of glucose use. J Clin Oncol Off J Am Soc Clin Oncol 21(14):2651–2657. doi:10.1200/JCO.2003.12.004
Wells P, Jones T, Price P (2003) Assessment of inter- and intrapatient variability in C15O2 positron emission tomography measurements of blood flow in patients with intra-abdominal cancers. Clin Cancer Res Off J Am Assoc Cancer Res 9(17):6350–6356
Wilkinson MD, Fulham MJ, Heard RN, McCaughan BC, McCarthy SW (2003) FDG-PET in paraneoplastic neuropathy. Neurology 60(10):1668
Wilson CB, Lammertsma AA, McKenzie CG, Sikora K, Jones T (1992) Measurements of blood flow and exchanging water space in breast tumors using positron emission tomography: a rapid and noninvasive dynamic method. Cancer Res 52(6):1592–1597
Withofs N, Bernard C, Van der Rest C, Martinive P, Hatt M, Jodogne S, Visvikis D, Lee JA, Coucke PA, Hustinx R (2014) FDG PET/CT for rectal carcinoma radiotherapy treatment planning: comparison of functional volume delineation algorithms and clinical challenges. J Appl Clin Med Phys/Am Coll Med Phys 15(5):4696. doi:10.1120/jacmp.v15i5.4696
Yoon HJ, Kang KW, Chun IK, Cho N, Im SA, Jeong S, Lee S, Jung KC, Lee YS, Jeong JM, Lee DS, Chung JK, Moon WK (2014) Correlation of breast cancer subtypes, based on estrogen receptor, progesterone receptor, and HER2, with functional imaging parameters from (6)(8)Ga-RGD PET/CT and (1)(8)F-FDG PET/CT. Eur J Nucl Med Mol Imaging 41(8):1534–1543. doi:10.1007/s00259-014-2744-4
Yu EY, Mankoff DA (2007) Positron emission tomography imaging as a cancer biomarker. Expert Rev Mol Diagn 7(5):659–672. doi:10.1586/14737159.7.5.659
Zhou X, Chen R, **e W, Ni Y, Liu J, Huang G (2014) Relationship between 18F-FDG accumulation and lactate dehydrogenase a expression in lung adenocarcinomas. J Nucl Med Off Publ Soc Nucl Med. doi:10.2967/jnumed.114.145490
Zimny M, Gagel B, DiMartino E, Hamacher K, Coenen HH, Westhofen M, Eble M, Buell U, Reinartz P (2006) FDG–a marker of tumour hypoxia? A comparison with [18F]fluoromisonidazole and pO2-polarography in metastatic head and neck cancer. Eur J Nucl Med Mol Imaging 33(12):1426–1431. doi:10.1007/s00259-006-0175-6
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Apostolova, I., Wedel, F., Brenner, W. (2016). Imaging of Tumor Metabolism Using Positron Emission Tomography (PET). In: Cramer, T., A. Schmitt, C. (eds) Metabolism in Cancer. Recent Results in Cancer Research, vol 207. Springer, Cham. https://doi.org/10.1007/978-3-319-42118-6_8
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