Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Molecular imaging of tumor metabolism and apoptosis

Abstract

Increased metabolism in a number of cellular pathways is a common feature of malignant tumors. This metabolic hallmark of neoplastic tissue led to the development of radiopharmaceuticals for the assessment of transport and enzymatic activity for tumor diagnosis and staging. The malignant transformation causes the activation of oncogenic proteins and signaling pathways that stimulate glycolysis. The resulting high-glucose metabolism of cancer cells allows PET imaging using FDG. Other molecules frequently applied in preclinical and clinical studies are 11C-methionine, tyrosine analogs and choline-based tracers. Using quantitative procedures they enable therapy monitoring by assessment of changes in transport and metabolization. As apoptosis is an important mechanism of cell death in tumors responding to treatment, non-invasive assessment of apoptosis using tracers for detection of phosphatidyl-serine presentation and/or caspase activation could be used as a surrogate marker for therapeutic efficacy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  • Aboagye EO, Bhujwalla ZM . (1999). Malignant transformation alters membrane choline phospholipid metabolism of human mammary epithelial cells. Cancer Res 59: 80–84.

    CAS  PubMed  Google Scholar 

  • Ackerstaff E, Glunde K, Bhujwalla ZM . (2003). Choline phospholipid metabolism: a target in cancer cells? J Cell Biochem 90: 525–533.

    CAS  PubMed  Google Scholar 

  • Bassa P, Kim EE, Inoue T, Wong FC, Korkmaz M, Yang DJ et al. (1996). Evaluation of preoperative chemotherapy using PET with fluorine-18-fluorodeoxyglucose in breast cancer. J Nucl Med 37: 931–938.

    CAS  PubMed  Google Scholar 

  • 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: 1066–1074.

    CAS  PubMed  Google Scholar 

  • Bergstrom M, Muhr C, Lundberg PO, Bergström K, Gee AD, Fasth KJ 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: 815–819.

    CAS  PubMed  Google Scholar 

  • 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 USA 95: 6349–6354.

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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: 184–191.

    CAS  PubMed  Google Scholar 

  • Bogin L, Papa MZ, Polak-Charcon S, Degani H . (1998). TNF-induced modulations of phospholipid metabolism in human breast cancer cells. Biochim Biophys Acta 1392: 217–232.

    CAS  PubMed  Google Scholar 

  • 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: 556–565.

    CAS  PubMed  Google Scholar 

  • Busch H, Davis JR, Honig GR, Anderson DC, Nair PV, Nyhan WL et al. (1959). The uptake of a variety of amino acids into nuclear proteins of tumors and other tissues. Cancer Res 19: 1030–1039.

    CAS  PubMed  Google Scholar 

  • Cai H, Erhardt P, Troppmair J, Diaz-Meco MT, Sithanandam G, Rapp UR et al. (1993). Hydrolysis of phosphatidylcholine couples Ras to activation of Raf protein kinase during mitogenic signal transduction. Mol Cell Biol 13: 7645–7651.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Christensen HN . (1990). Role of amino acid transport and countertransport in nutrition and metabolism. Physiol Rev 70: 43–76.

    CAS  PubMed  Google Scholar 

  • Cuadrado A, Carnero A, Dolfi F, Jimenez B, Lacal JC . (1993). Phosphorylcholine: a novel second messenger essential for mitogenic activity of growth factors. Oncogene 8: 2959–2968.

    CAS  PubMed  Google Scholar 

  • Cuadrado A, Issing W, Fleming TP, Molloy CJ . (1994). Uneven distribution of protein kinase C-a and -b isozymes in human sarcomas and carcinomas. J Cell Physiol 159: 434–440.

    CAS  PubMed  Google Scholar 

  • Daemen BJ, Elsinga PH, Mooibroek J, Paans AM, Wieringa AR, Konings AW 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: 1587–1592.

    CAS  PubMed  Google Scholar 

  • de Certaines JD, Larsen VA, Podo F, Carpinelli G, Briot O, Henriksen O . (1993). In vivo 31P MRS of experimental tumours. NMR Biomed 6: 345–365.

    CAS  PubMed  Google Scholar 

  • DeGrado TL, Coleman RE, Wang S, Baldwin SW, Orr MD, Robertson CN et al. (2000). Price synthesis and evaluation of 18F-labeled choline as an oncologic tracer for positron emission tomography: initial findings in prostate cancer. Cancer Res 61: 110–117.

    Google Scholar 

  • DeGrado TR, Coleman RE, Wang S, Baldwin SW, Orr MD, Robertson CN et al. (2001). Synthesis and evaluation of (18)F-labeled choline analogs as oncologic PET tracers. J Nucl Med 42: 1805–1814.

    CAS  PubMed  Google Scholar 

  • Dunzendorfer U, Schmall B, Bigler RE, Zanzonico PB, Conti PS, Dahl JR 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: 535–538.

    CAS  PubMed  Google Scholar 

  • 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: 1492–1495.

    CAS  PubMed  Google Scholar 

  • Galetic I, Andjelkovic M, Meier R, Brodbeck D, Park J, Hemmings BA . (1999). Mechanism of protein kinase B activation by insulin/insulin-like growth factor-1 revealed by specific inhibitors of phosphoinositide 3-kinase—significance for diabetes and cancer. Pharmacol Ther 82: 409–425.

    CAS  PubMed  Google Scholar 

  • Galons JP, Job C, Gillies RJ . (1995). Increase of GPC levels in cultured mammalian cells during acidosis. A 31P MR spectroscopy study using a continuous bioreactor system. Magn Reson Med 33: 422–426.

    CAS  PubMed  Google Scholar 

  • Gallagher BM, Ansari A, Atkins H, Casella V, Christman DR et al. (1977). 18F-labeled 2-deoxy-2-fluoro-D-glucose as a radiopharmaceutical for measuring regional myocardial glucose metabolism in vivo: tissue distribution and imaging studies in animals. J Nucl Med 18: 990–996.

    CAS  PubMed  Google Scholar 

  • Ganapathy V, Thangaraju M, Prasad PD . (2009). Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond. Pharmacol Ther 121: 29–40.

    CAS  PubMed  Google Scholar 

  • Gribbestad IS, Sitter B, Lundgren S, Krane J, Axelson D . (1999). Metabolite composition in breast tumors examined by proton nuclear magnetic resonance spectroscopy. Anticancer Res 19: 1737–1746.

    CAS  PubMed  Google Scholar 

  • Guthridge CJ, Stampfer MR, Clark MA, Steiner MR . (1994). Phospholipases A2 in ras-transformed and immortalized human mammary epithelial cells. Cancer Lett 86: 11–21.

    CAS  PubMed  Google Scholar 

  • Haberkorn U, Altmann A, Kamencic H, Morr I, Traut U, Henze M et al. (2001a). Glucose transport and apoptosis after gene therapy with HSV thymidine kinase. Eur J Nucl Med 28: 1690–1696.

    CAS  PubMed  Google Scholar 

  • Haberkorn U, Altmann A, Morr I, Germann C, Oberdorfer F, van Kaick G . (1997a). Multi tracer studies during gene therapy of hepatoma cells with HSV thymidine kinase and ganciclovir. J Nucl Med 38: 1048–1054.

    CAS  PubMed  Google Scholar 

  • Haberkorn U, Bellemann ME, Altmann A, Gerlach L, Morr I, Oberdorfer F et al. (1997b). PET 2-fluoro-2-deoxyglucose uptake in rat prostate adenocarcinoma during chemotherapy with gemcitabine. J Nucl Med 38: 1215–1221.

    CAS  PubMed  Google Scholar 

  • Haberkorn U, Bellemann ME, Brix G, Kamencic H, Morr I, Traut U et al. (2001b). Apoptosis and changes in glucose transport early after treatment of Morris hepatoma with gemcitabine. Eur J Nucl Med 28: 418–425.

    CAS  PubMed  Google Scholar 

  • Haberkorn U, Bellemann ME, Gerlach L, Morr I, Trojan H, Brix G et al. (1998). Uncoupling of 2-fluoro-2-deoxyglucose transport and phosphorylation in rat hepatoma during gene therapy with HSV thymidine kinase. Gene Ther 5: 880–887.

    CAS  PubMed  Google Scholar 

  • 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: 793–798.

    CAS  PubMed  Google Scholar 

  • Haberkorn U, Mier W, Eisenhut M . (2005). Scintigraphic imaging of gene expression and gene transfer. Curr Med Chem 12: 779–794.

    CAS  PubMed  Google Scholar 

  • Haberkorn U, Reinhardt M, Strauss LG, Oberdorfer F, Berger MR, Altmann A et al. (1992). Metabolic design of combination therapy: use of enhanced fluorodeoxyglucose uptake caused by chemotherapy. J Nucl Med 33: 1981–1987.

    CAS  PubMed  Google Scholar 

  • Haberkorn U, Strauss LG, Dimitrakopoulou A, Engenhart R, Oberdorfer F, Ostertag H et al. (1991). PET studies of fluorodeoxyglucose metabolism in patients with recurrent colorectal tumors receiving radiotherapy. J Nucl Med 32: 1485–1490.

    CAS  PubMed  Google Scholar 

  • Haberkorn U, Strauss LG, Dimitrakopoulou A, Seiffert E, Oberdorfer F, Ziegler S et al. (1993). Fluorodeoxyglucose imaging of advanced head and neck cancer after chemotherapy. J Nucl Med 34: 12–17.

    CAS  PubMed  Google Scholar 

  • Haberkorn U, Ziegler SI, Oberdorfer F, Trojan H, Haag D, Peschke P et al. (1994). FDG uptake, tumor proliferation and expression of glycolysis associated genes in animal tumor models. Nucl Med Biol 21: 827–834.

    CAS  PubMed  Google Scholar 

  • Haeffner EW . (1975). Studies on choline permeation through the plasma membrane and its incorporation into phosphatidyl choline of Ehrlich–Lettré-ascites tumor cells in vitro. Eur J Biochem 51: 219–228.

    CAS  PubMed  Google Scholar 

  • Hara T, Kosaka N, Kishi H . (1998). PET imaging of prostate cancer using carbon-11-choline. J Nucl Med 39: 990–995.

    CAS  PubMed  Google Scholar 

  • Hara T, Kosaka N, Kishi H . (2002). Development of (18)F-fluoroethylcholine for cancer imaging with PET: synthesis, biochemistry, and prostate cancer imaging. J Nucl Med 43: 187–199.

    CAS  PubMed  Google Scholar 

  • 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: 881–887.

    CAS  PubMed  Google Scholar 

  • Heiss P, Mayer S, Herz M, Wester HJ, Schwaiger M, Senekowitsch-Schmidtke R . (1999). Investigation of transport mechanism and uptake kinetics of O-(2-[18F]fluoroethyl)-L-tyrosine in vitro and in vivo. J Nucl Med 40: 1367–1373.

    CAS  PubMed  Google Scholar 

  • Hernandez-Alcoceba R, Fernandez F, Lacal JC . (1999). In vivo antitumor activity of choline kinase inhibitors: a novel target for anticancer drug discovery. Cancer Res 59: 3112–3118.

    CAS  PubMed  Google Scholar 

  • 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: 773–779.

    CAS  PubMed  Google Scholar 

  • Hughes CS, Shen JW, Subjeck JR . (1989). Resistance to etoposide induced by three glucose-regulated stresses in Chinese hamster ovary cells. Cancer Res 49: 4452–4454.

    CAS  PubMed  Google Scholar 

  • Ishiwata K, Enomoto K, Sasaki T, Elsinga PH, Senda M, Okazumi S 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: 279–285.

    CAS  PubMed  Google Scholar 

  • Isselbacher KJ . (1972). Sugar and amino acid transport by cells in culture: differences between normal and malignant cells. N Engl J Med 286: 929–933.

    CAS  PubMed  Google Scholar 

  • Jager PL, Vaalburg W, Pruim J, de Vries EG, Langen KJ, Piers DA . (2001). Radiolabeled amino acids: basic aspects and clinical applications in oncology. J Nucl Med 42: 432–445.

    CAS  PubMed  Google Scholar 

  • Jansson T, Westlin JE, Ahlstrom H, Lilja A, LÃ¥ngström B, Bergh J 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: 1470–1477.

    CAS  PubMed  Google Scholar 

  • Katz-Brull R, Degani H . (1996). Kinetics of choline transport and phosphorylation in human breast cancer cells; NMR application of the zero trans method. Anticancer Res 16: 1375–1380.

    CAS  PubMed  Google Scholar 

  • Kiss Z, Crilly KS, Anderson WH . (1993). Carcinogens stimulate phosphorylation of ethanolamine derived from increased hydrolysis of phosphatidylethanolamine in C3H/101/2 fibroblasts. FEBS Lett 336: 115–118.

    CAS  PubMed  Google Scholar 

  • Kobori O, Kirihara Y, Kosaka N, Hara T . (1999). Positron emission tomography of esophageal carcinoma using 11C-choline and 18F-fluorodeoxyglucose. Cancer 86: 1638–1648.

    CAS  PubMed  Google Scholar 

  • Kurhanewicz J, Vigneron DB, Nelson SJ . (2000). Threedimensional magnetic resonance spectroscopic imaging of brain and prostate cancer. Neoplasia 2: 166–189.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kuwert T, Probst-Cousin S, Woesler B, Morgenroth C, Lerch H, Matheja P et al. (1997). Iodine-123-alpha-methyl tyrosine in glioma: correlation with cellular density and proliferative activity. J Nucl Med 38: 1551–1555.

    CAS  PubMed  Google Scholar 

  • Kwee SA, Coel MN, Lim J, Ko JP . (2004). Combined use of F-18 fluorocholine positron emission tomography and magnetic resonance spectroscopy for brain tumor evaluation. J Neuroimaging 14: 285–289.

    PubMed  Google Scholar 

  • Kwee SA, Wei H, Sesterhenn I, Yun D, Coel MN . (2006). Localization of primary prostate cancer with dual-phase 18F-fluorocholine PET. J Nucl Med 47: 262–269.

    PubMed  Google Scholar 

  • Kypta RM, Goldberg Y, Ulug ET, Courtneidge SA . (1990). Association between the PDGF receptor and members of the src family of tyrosine kinases. Cell 62: 481–492.

    CAS  PubMed  Google Scholar 

  • Langen KJ, Ziemons K, Kiwit JC, Herzog H, Kuwert T, Bock WJ 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: 517–522.

    CAS  PubMed  Google Scholar 

  • Leach MO, Verrill M, Glaholm J, Smith TA, Collins DJ, Payne GS et al. (1998). Measurements of human breast cancer using magnetic resonance spectroscopy: a review of clinical measurements and a report of localized 31P measurements of response to treatment. NMR Biomed 11: 314–340.

    CAS  PubMed  Google Scholar 

  • Li X, Lu Y, Pirzkall A, McKnight T, Nelson SJ . (2002). Analysis of the spatial characteristics of metabolic abnormalities in newly diagnosed glioma patients. J Magn Reson Imaging 16: 229–237.

    PubMed  Google Scholar 

  • Lindholm P, Leskinen S, Lapela M . (1998). Carbon-11-methionine uptake in squamous cell head and neck cancer. J Nucl Med 39: 1393–1397.

    CAS  PubMed  Google Scholar 

  • Machado de Domenech EE, Sols A . (1980). Specificity of hexokinases towards some uncommon substrates and inhibitors. FEBS Lett 119: 174–176.

    CAS  PubMed  Google Scholar 

  • 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: 1545–1556.

    CAS  PubMed  Google Scholar 

  • McConathy J, Martarello L, Malveaux EJ, Camp VM, Simpson NE, Simpson CP 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: 2240–2249.

    CAS  PubMed  Google Scholar 

  • Molloy CJ, Bottaro DP, Fleming TP, Marshall MS, Gibbs JB, Aaronson SA . (1989). PDGF induction of tyrosine phosphorylation of GTPase activating protein. Nature (Lond) 342: 711–714.

    CAS  Google Scholar 

  • Negendank W . (1992). Studies of human tumors by MRS: a review. NMR Biomed 5: 303–324.

    CAS  PubMed  Google Scholar 

  • Noh DY, Ahn SJ, Lee RA, Park IA, Kim JH, Suh PG et al. (2000). Overexpression of phospholipase D1 in human breast cancer tissues. Cancer Lett 161: 207–214.

    CAS  PubMed  Google Scholar 

  • Ogawa T, Kanno I, Shishido F, Inugami A, Higano S, Fujita H 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: 197–202.

    CAS  PubMed  Google Scholar 

  • Pauleit D, Floeth F, Hamacher K, Riemenschneider MJ, Reifenberger G, Müller HW et al. (2005). O-(2-[18F]fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas. Brain 128: 678–687.

    PubMed  Google Scholar 

  • Pöpperl G, Götz C, Rachinger W, Gildehaus FJ, Tonn JC, Tatsch K . (2004). Value of O-(2-[18F]fluoroethyl)-L-tyrosine PET for the diagnosis of recurrent glioma. Eur J Nucl Med Mol Imaging 31: 1464–1470.

    PubMed  Google Scholar 

  • Ramirez de Molina A, Gutierrez R, Ramos MA, Silva JM, Silva J, Bonilla F et al. (2002a). Increased choline kinase activity in human breast carcinomas: clinical evidence for a potential novel antitumor strategy. Oncogene 21: 4317–4322.

    CAS  PubMed  Google Scholar 

  • Ramirez de Molina A, Rodriguez-Gonzalez A, Gutierrez R, Martinez-Pineiro L, Sanchez J, Bonilla F et al. (2002b). Overexpression of choline kinase is a frequent feature in human tumor-derived cell lines and in lung, prostate, and colorectal human cancers. Biochem Biophys Res Commun 296: 580–583.

    CAS  PubMed  Google Scholar 

  • Rau FC, Weber WA, Wester HJ, Herz M, Becker I, Krüger A 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: 1039–1046.

    CAS  Google Scholar 

  • Ronen SM, Jackson LE, Beloueche M, Leach MO . (2001). Magnetic resonance detects changes in phosphocholine associated with Ras activation and inhibition in NIH 3T3 cells. Br J Cancer 84: 691–696.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rozental JM, Levine RL, Nickles RJ, Dobkin JA . (1989). Glucose uptake by gliomas after treatment. A positron emission tomographic study. Arch Neurol 46: 1302–1307.

    CAS  PubMed  Google Scholar 

  • 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: 1–20.

    CAS  PubMed  Google Scholar 

  • Salber D, Stoffels G, Pauleit D, Oros-Peusquens AM, Shah NJ, Klauth P et al. (2007). Differential uptake of O-(2-18F-fluoroethyl)-L-tyrosine, L-3H-methionine, and 3H-deoxyglucose in brain abscesses. J Nucl Med 48: 2056–2062.

    CAS  PubMed  Google Scholar 

  • Scanlon K, Cashmore AR, Kashani-Sabet M, Pallai M, Dreyer RN, Moroson BA et al. (1987). Inhibition of methionine uptake by methotrexate in mouse leukemia L1210. Cancer Chemother Pharmacol 19: 21–24.

    CAS  PubMed  Google Scholar 

  • Scanlon K, Safirstein RL, Thies H, Gross RB, Waxman S, Guttenplan JB . (1983). Inhibition of amino acid transport by cis-diaminedichloroplatinum (II) derivatives L1210 murine leukemia cells. Cancer Res 43: 4211–4215.

    CAS  PubMed  Google Scholar 

  • Schaider H, Haberkorn U, Berger MR, Oberdorfer F, Morr I, van Kaick G . (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: 55–60.

    CAS  PubMed  Google Scholar 

  • 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: 2112–2118.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shoup TM, Olson J, Hoffman JM, Votaw J, Eshima D, Eshima L et al. (1999). Synthesis and evaluation of [18F]1-amino-3-fluorocyclobutane-1-carboxylic acid to image brain tumors. J Nucl Med 40: 331–338.

    CAS  PubMed  Google Scholar 

  • Sieger S, Jiang S, Kleinschmidt J, Eskerski H, Schönsiegel F, Altmann A et al. (2004). Tumor-specific gene expression using regulatory elements of the glucose transporter isoform 1 gene. Cancer Gene Ther 11: 41–51.

    CAS  PubMed  Google Scholar 

  • Sieger S, Jiang S, Schönsiegel F, Eskerski H, Kübler W, Altmann A et al. (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: 748–756.

    CAS  PubMed  Google Scholar 

  • Singh D, Banerji AK, Dwarakanath BS, Tripathi RP, Gupta JP, Mathew TL et al. (2005). Optimizing cancer radiotherapy with 2-deoxy-d-glucose dose escalation studies in patients with glioblastoma multiforme. Strahlenther Onkol 181: 507–514.

    PubMed  Google Scholar 

  • Sols A, Crane RK . (1954). Substrate specificity of brain hexokinase. J Biol Chem 210: 581–595.

    CAS  PubMed  Google Scholar 

  • Uehara H, Miyagawa T, Tjuvajev J, Joshi R, Beattie B, Oku T 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: 1239–1253.

    CAS  PubMed  Google Scholar 

  • Vaalburg W, Coenen HH, Crouzel C, Elsinga PH, LÃ¥ngström B, Lemaire C et al (1992). Amino acids for the measurement of protein synthesis in vivo by PET. Int J Rad Appl Instrum B 19: 227–237.

    CAS  PubMed  Google Scholar 

  • Vansteenkiste JF, Stroobants SG, Dupont PJ, De Leyn PR, Verbeken EK, Deneffe GJ 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: 3201–3206.

    CAS  PubMed  Google Scholar 

  • Vees H, Senthamizhchelvan S, Miralbell R, Weber DC, Ratib O, Zaidi H . (2009). Assessment of various strategies for 18F-FET PET-guided delineation of target volumes in high-grade glioma patients. Eur J Nucl Med Mol Imaging 36: 182–193.

    PubMed  Google Scholar 

  • Villa P, Kaufmann SH, Earnshwa WC . (1997). Caspases and caspase inhibitors. TIBS 22: 388–393.

    CAS  PubMed  Google Scholar 

  • 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 USA 88: 2525–2529.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wester HJ, Herz M, Weber W, Heiss P, Senekowitsch-Schmidtke R, Schwaiger M et al. (1999). Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor imaging. J Nucl Med 40: 205–212.

    CAS  PubMed  Google Scholar 

  • Widnell CC, Baldwin SA, Davies A, Martin S, Pasternak CA . (1990). Cellular stress induces a redistribution of the glucose transporter. FASEB J 4: 1634–1637.

    CAS  PubMed  Google Scholar 

  • Wienhard K, Herholz K, Coenen HH, Rudolf J, Kling P, Stöcklin G et al. (1991). Increased amino acid transport into brain tumors measured by PET of L-(2-18F)fluorotyrosine. J Nucl Med 32: 1338–1346.

    CAS  PubMed  Google Scholar 

  • Willemsen AT, vanWaarde A, Paans AM, Pruim J, Luurtsema G, Go KG 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: 411–419.

    CAS  PubMed  Google Scholar 

  • Wurker M, Herholz K, Voges J, Pietrzyk U, Treuer H, Bauer B et al. (1996). Glucose consumption and methionine uptake in low-grade gliomas after iodine-125 brachytherapy. Eur J Nucl Med 23: 583–586.

    CAS  PubMed  Google Scholar 

  • Zhou D, Chu W, Chen DL, Wang Q, Reichert DE, Rothfuss J et al. (2009). 18F and 11C-labeled N-benzyl-isatin sulfonamide analogues as PET tracers for apoptosis: synthesis, radiolabelling mechanism, and in vivo imaging study of apoptosis in Fas-treated mice using 11C-WC-98. Org BiomolChem 7: 1337–1348.

    CAS  Google Scholar 

  • Zwaal RFA, Schroit AJ . (1997). Pathophysiologic implications of membrane phospholipid asymmetry in blood cells. Blood 89: 1121–1132.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to U Haberkorn.

Ethics declarations

Competing interests

The authors declare no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Haberkorn, U., Markert, A., Mier, W. et al. Molecular imaging of tumor metabolism and apoptosis. Oncogene 30, 4141–4151 (2011). https://doi.org/10.1038/onc.2011.169

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/onc.2011.169

Keywords

This article is cited by

Search

Quick links