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Positron Emission Tomography Measurement of Tumor Metabolism and Growth: Its Expanding Role in Oncology

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Abstract

This work highlights the explosion and evolution of positron emission tomography (PET) for use in oncology research and clinical practice. 2-Deoxy-2-[F-18]fluoro-d-glucose (FDG)-PET is important in the staging of cancer, estimation of prognosis, and for its ability to predict therapeutic outcome. A number of new imaging agents are under development and may find a place in oncology when studies prove their utility. This scientific overview includes a review of the development of a number of thymidine analogs, such as 18F-3′-deoxy-3′-fluorothymidine (FLT) and 18F-1-(2′-deoxy-2′-fluoro-beta-d-arabinofuranosyl)-thymine (FMAU), including chemical structure variations; their application in a variety of tumors; and the role of various kinetic models for understanding cellular proliferation. The greatest unmet need for PET is in further developing and validating its use in the measurement of treatment response.

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References

  1. Henschke CI (2005) CT screening for lung cancer: Update 2005. Surg Oncol Clin N Am 14(4):761–776

    Article  PubMed  Google Scholar 

  2. Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47:207–214 (Jan 1)

    Article  PubMed  CAS  Google Scholar 

  3. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–216

    Article  PubMed  CAS  Google Scholar 

  4. Valk PE, Bailey DL, Townsend DW, Maisey MN (2003) Positron emission tomography. London: Springer-Verlag

  5. Hamid O, Varterasian ML, Wadler S, Hecht JR, Benson A, 3rd, Galanis E, et al. (2003) Phase II trial of intravenous CI-1042 in patients with metastatic colorectal cancer. J Clin Oncol 21(8):1498–1504

    Article  PubMed  CAS  Google Scholar 

  6. Toloza EM, Harpole L, McCrory DC (2003) Noninvasive staging of non-small cell lung cancer: A review of the current evidence. Chest 123(1 Suppl):137S–146S

    Article  PubMed  Google Scholar 

  7. Fernandez FG, Drebin JA, Linehan DC, Dehdashti F, Siegel BA, Strasberg SM (2004) Five-year survival after resection of hepatic metastases from colorectal cancer in patients screened by positron emission tomography with F-18 fluorodeoxyglucose (FDG-PET). Ann Surg 240(3):438–47; discussion 447–450

    Google Scholar 

  8. Bill-Axelson A, Holmberg L, Ruutu M, Haggman M, Andersson SO, Bratell S, et al. (2005) Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 352(19):1977–1984

    Article  PubMed  CAS  Google Scholar 

  9. Choi JY, Jang HJ, Shim YM, Kim K, Lee KS, Lee KH, et al. (2004) 18F-FDG-PET in patients with esophageal squamous cell carcinoma undergoing curative surgery: Prognostic implications. J Nucl Med 45(11):1843–1850

    PubMed  Google Scholar 

  10. Sasaki R, Komaki R, Macapinlac H, Erasmus J, Allen P, Forster K, et al. (2005) [18F]Fluorodeoxyglucose uptake by positron emission tomography predicts outcome of non-small-cell lung cancer. J Clin Oncol 23(6):1136–1143

    Article  PubMed  CAS  Google Scholar 

  11. Schwarzbach MH, Hinz U, Dimitrakopoulou-Strauss A, Willeke F, Cardona S, Mechtersheimer G, et al. (2005) Prognostic significance of preoperative [18-F]fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging in patients with resectable soft tissue sarcomas. Ann Surg 241(2):286–294

    Article  PubMed  Google Scholar 

  12. 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(10):3201–3206

    PubMed  CAS  Google Scholar 

  13. Burge CN, Chang HR, Apple SK (2005) Do the histologic features and results of breast cancer biomarker studies differ between core biopsy and surgical excision specimens? Breast

  14. de Vos tot Nederveen Cappel WH, Meulenbeld HJ, Kleibeuker JH, Nagengast FM, Menko FH, Griffioen G, et al. (2004) Survival after adjuvant 5-FU treatment for stage III colon cancer in hereditary nonpolyposis colorectal cancer. Int J Cancer 109(3): 468–471

    Article  Google Scholar 

  15. Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, et al. (2003) Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 349(3):247–257

    Article  PubMed  CAS  Google Scholar 

  16. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 350(21):2129–2139

    Article  PubMed  CAS  Google Scholar 

  17. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, et al. (2004) EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science 304(5676):1497–1500

    Article  PubMed  CAS  Google Scholar 

  18. Dehdashti F, Mortimer JE, Siegel BA, Griffeth LK, Bonasera TJ, Fusselman MJ, et al. (1995) Positron tomographic assessment of estrogen receptors in breast cancer: Comparison with FDG-PET and in vitro receptor assays. J Nucl Med 36(10):1766–1774

    PubMed  CAS  Google Scholar 

  19. Linden HM, Stekhova S, Link JM, Gralow JR, Livingston RB, Ellis GK, et al. (2004) HER2 expression and uptake of 18F-fluoroestradiol predict response of breast cancer to hormonal therapy. J Nucl Med 45:85–86P

    Google Scholar 

  20. Fricke E, Machtens S, Hofmann M, van den Hoff J, Bergh S, Brunkhorst T, et al. (2003) Positron emission tomography with 11C-acetate and 18F-FDG in prostate cancer patients. Eur J Nucl Med Mol Imaging 30(4):607–611

    PubMed  CAS  Google Scholar 

  21. Dehdashti F, Grigsby PW, Mintun MA, Lewis JS, Siegel BA, Welch MJ (2003) Assessing tumor hypoxia in cervical cancer by positron emission tomography with 60Cu-ATSM: Relationship to therapeutic response—a preliminary report. Int J Radiat Oncol Biol Phys 55(5): 1233–1238

    PubMed  Google Scholar 

  22. Eschmann SM, Paulsen F, Reimold M, Dittmann H, Welz S, Reischl G, et al. (2005) Prognostic impact of hypoxia imaging with 18F-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy. J Nucl Med 46(2):253–260

    PubMed  Google Scholar 

  23. Koh WJ, Bergman KS, Rasey JS, Peterson LM, Evans ML, Graham MM, et al. (1995) Evaluation of oxygenation status during fractionated radiotherapy in human nonsmall cell lung cancers using [F-18]fluoromisonidazole positron emission tomography. Int J Radiat Oncol Biol Phys 33(2):391–398

    PubMed  CAS  Google Scholar 

  24. O'Donoghue JA, Zanzonico P, Pugachev A, Wen B, Smith-Jones P, Cai S, et al. (2005) Assessment of regional tumor hypoxia using 18F-fluoromisonidazole and 64Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) positron emission tomography: Comparative study featuring microPET imaging, Po2 probe measurement, autoradiography, and fluorescent microscopy in the R3327-AT and FaDu rat tumor models. Int J Radiat Oncol Biol Phys 61(5):1493–1502

    PubMed  Google Scholar 

  25. Weber WA, Wester HJ, Grosu AL, Herz M, Dzewas B, Feldmann HJ, et al. (2000) O-(2-[18F]Fluoroethyl)-l-tyrosine and l-[methyl-11C]methionine uptake in brain tumours: Initial results of a comparative study. Eur J Nucl Med 27(5):542–549

    Article  PubMed  CAS  Google Scholar 

  26. Pauleit D, Floeth F, Tellmann L, Hamacher K, Hautzel H, Muller HW, et al. (2004) Comparison of O-(2-18F-fluoroethyl)-l-tyrosine PET and 3-123I-iodo-alpha-methyl-l-tyrosine SPECT in brain tumors. J Nucl Med 45(3):374–381

    PubMed  CAS  Google Scholar 

  27. Oyama N, Miller TR, Dehdashti F, Siegel BA, Fischer KC, Michalski JM, et al. (2003) 11C-acetate PET imaging of prostate cancer: Detection of recurrent disease at PSA relapse. J Nucl Med 44(4):549–555

    PubMed  CAS  Google Scholar 

  28. Price DT, Coleman RE, Liao RP, Robertson CN, Polascik TJ, DeGrado TR (2002) Comparison of [18F]fluorocholine and [18F]fluorodeoxyglucose for positron emission tomography of androgen dependent and androgen independent prostate cancer. J Urol 168(1):273–280

    Article  PubMed  Google Scholar 

  29. Tian M, Zhang H, Oriuchi N, Higuchi T, Endo K (2004) Comparison of 11C-choline PET and FDG-PET for the differential diagnosis of malignant tumors. Eur J Nucl Med Mol Imaging 31(8):1064–1072

    Article  PubMed  CAS  Google Scholar 

  30. Yoshimoto M, Waki A, Yonekura Y, Sadato N, Murata T, Omata N, et al. (2001) Characterization of acetate metabolism in tumor cells in relation to cell proliferation: Acetate metabolism in tumor cells. Nucl Med Biol 28(2):117–122

    Article  PubMed  CAS  Google Scholar 

  31. Christman D, Crawford EJ, Friedkin M, Wolf AP (1972) Detection of DNA synthesis in intact organisms with positron-emitting [methyl-11C]thymidine. Proc Nat Acad Sci USA 69(4)

  32. Heidelberger C, Chaudhuri NK, Danneberg P, et al. (1957) Fluorinated pyrimidines, a new class of tumor-inhibitory compounds. Nature 179:663

    Article  PubMed  CAS  Google Scholar 

  33. Eary JF, Mankoff DA, Spence AM, Berger MS, Olshen A, Link JM, et al. (1999) 2-[C-11]Thymidine imaging of malignant brain tumors. Cancer Res 59(3):615–621

    PubMed  CAS  Google Scholar 

  34. Martiat P, Ferrant A, Labar D, Cogneau M, Bol A, Michel C, et al. (1988) In vivo measurement of carbon-11 thymidine uptake in non-Hodgkin's lymphoma using positron emission tomography. J Nucl Med 29:1633–1637

    PubMed  CAS  Google Scholar 

  35. Shields A, Dohmen B, Mangner T, Lawhorn-Crews J, Machulla H-J, Muzik O, et al. (2000) Imaging of thoracic tumors with [18F]FLT. J Nucl Med 74P

  36. Vander Borght T, Pauwels S, Lambotte L, Labar D, De Maeght S, Stroobandt G, et al. (1994) Brain tumor imaging with PET and 2-[carbon-11]thymidine. J Nucl Med 35(6):974–982

    Google Scholar 

  37. Gunn RN, Yap JT, Wells P, Osman S, Price P, Jones T, et al. (2000) A general method to correct PET data for tissue metabolites using a dual-scan approach. J Nucl Med 41(4):706–711

    PubMed  CAS  Google Scholar 

  38. Mankoff DA, Shields AF, Graham MM, Link JM, Eary JF, Krohn KA (1998) Kinetic analysis of 2-[carbon-11]thymidine PET imaging studies: Compartmental model and mathematical analysis. J Nucl Med 39(6):1043–1055

    PubMed  CAS  Google Scholar 

  39. Shields A, Briston D, Chandupatla S, Douglas K, Lawhorn-Crews J, Collins J, et al. (2005) A simplified analysis of [F-18]3′-fluorothymidine metabolism and retention. Eur J Nucl Med Mol Imaging 32:1269–1275

    PubMed  CAS  Google Scholar 

  40. Langen P, Etzold G, Hintsche R, G. K (1969) 3′-Deoxy-3′-fluorothymidine, a new selective inhibitor of DNA-synthesis. Acta Biol Med Ger 23(6):759–766

    PubMed  CAS  Google Scholar 

  41. Shields A, Grierson J, Stayanoff J, Lawhorn-Crews J, Obradovich J, Muzik O, et al. (1998) F-18 FLT can be used to image cell proliferation in vivo. J Nucl Med 39:228P

    Google Scholar 

  42. Buck AK, Schirrmeister H, Mattfeldt T, Reske SN (2004) Biological characterisation of breast cancer by means of PET. Eur J Nucl Med Mol Imaging 31(Suppl 1):S80–S87

    Article  PubMed  Google Scholar 

  43. Vesselle H, Grierson J, Muzi M, Pugsley JM, Schmidt RA, Rabinowitz P, et al. (2002) In vivo validation of 3′-deoxy-3′-[(18)F]fluorothymidine ([(18)F]FLT) as a proliferation imaging tracer in humans: Correlation of [(18)F]FLT uptake by positron emission tomography with Ki-67 immunohistochemistry and flow cytometry in human lung tumors. Clin Cancer Res 8(11):3315–3323

    PubMed  CAS  Google Scholar 

  44. van Westreenen HL, Cobben DC, Jager PL, van Dullemen HM, Wesseling J, Elsinga PH, et al. (2005) Comparison of 18F-FLT PET and 18F-FDG-PET in esophageal cancer. J Nucl Med 46(3): 400–404

    PubMed  Google Scholar 

  45. Gjedde A (1982) Calculation of cerebral glucose phosphorylation from brain uptake of glucose a1nalogs in vivo: A re-examination. Brain Res Rev 4:237–274

    Article  CAS  Google Scholar 

  46. Patlak CS, Blasberg RG, Fenstermacher JD (1983) Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 3:1–7

    PubMed  CAS  Google Scholar 

  47. Shields AF (2003) Labeled pyrimdines in PET imaging. In: Valk PE, Bailey DL, Townsend DW, Maisey MN (eds) Positron emission tomography. London: Springer-Verlag, pp 715–724

    Google Scholar 

  48. Buck AK, Halter G, Schirrmeister H, Kotzerke J, Wurziger I, Glatting G, et al. (2003) Imaging proliferation in lung tumors with PET: 18F-FLT versus 18F-FDG. J Nucl Med 44(9):1426–1431

    PubMed  CAS  Google Scholar 

  49. Chen W, Cloughesy T, Kamdar N, Satyamurthy N, Bergsneider M, Liau L, et al. (2005) Imaging proliferation in brain tumors with 18F-FLT PET: Comparison with 18F-FDG. J Nucl Med 46(6):945–952

    PubMed  CAS  Google Scholar 

  50. Francis DL, Visvikis D, Costa DC, Arulampalam TH, Townsend C, Luthra SK, et al. (2003) Potential impact of [18F]3′-deoxy-3′-fluorothymidine versus [18F]fluoro-2-deoxy-d-glucose in positron emission tomography for colorectal cancer. Eur J Nucl Med Mol Imaging 30(7):988–994

    Article  PubMed  CAS  Google Scholar 

  51. Conti P, Alauddin M, Fissekis J, Schmall B, Watanabe K (1995) Synthesis of 2′-fluoro-5-[11C]-methyl-1-beta-d-arabinofuranosyluracil ([11C]-FMAU): A potential nucleoside analog for in vivo study of cellular proliferation with PET. Nucl Med Biol 22:783–789 (Aug. 6)

    Article  PubMed  CAS  Google Scholar 

  52. Mangner T, Klecker R, Anderson L, Shields A (2003) Synthesis of 2′-[18F]fluoro-2′-deoxy-β-d-arabinofuranosyl nucleotides, [18F]FAU, [18F]FMAU, [18F]FBAU and [18F]FIAU, as potential pet agents for imaging cellular proliferation. Nucl Med Biol (30):215–224

    Article  PubMed  CAS  Google Scholar 

  53. Mangner TJ, Klecker R, Anderson L, Shields A (2001) Synthesis of 2′-[F-18]fluoro-2′-deoxy-β-d-arabinofuranosyl nucleosides. J Labelled Comp Radipharm 44:S912–S914

    Google Scholar 

  54. Sun H, Mangner TJ, Collins JM, Muzik O, Douglas K, Shields AF (2005) Imaging DNA synthesis in vivo with 18F-FMAU and PET. J Nucl Med 46(2):292–296

    PubMed  CAS  Google Scholar 

  55. Sun H, Sloan A, Mangner TJ, Vaishampayan U, Muzik O, Collins JM, et al. (2005) Imaging DNA synthesis with [18F]FMAU and positron emission tomography in patients with cancer. Eur J Nucl Med Mol Imaging 32(1):15–22

    Article  PubMed  CAS  Google Scholar 

  56. Stroobants S, Goeminne J, Seegers M, Dimitrijevic S, Dupont P, Nuyts J, et al. (2003) 18FDG-positron emission tomography for the early prediction of response in advanced soft tissue sarcoma treated with imatinib mesylate (Glivec). Eur J Cancer 39(14):2012–2020

    Article  PubMed  CAS  Google Scholar 

  57. Al-Sukhun S, Zalupski MM, Ben-Josef E, Vaitkevicius VK, Philip PA, Soulen R, et al. (2003) Chemoradiotherapy in the treatment of regional pancreatic carcinoma: A phase II study. Am J Clin Oncol 26(6):543–549

    Article  PubMed  CAS  Google Scholar 

  58. Kostakoglu L, Coleman M, Leonard JP, Kuji I, Zoe H, Goldsmith SJ (2002) PET predicts prognosis after 1 cycle of chemotherapy in aggressive lymphoma and Hodgkin's disease. J Nucl Med 43(8):1018–1027

    PubMed  Google Scholar 

  59. Mortimer JE, Dehdashti F, Siegel BA, Trinkaus K, Katzenellenbogen JA, Welch MJ (2001) Metabolic flare: Indicator of hormone responsiveness in advanced breast cancer. J Clin Oncol 19(11):2797–2803

    PubMed  CAS  Google Scholar 

  60. MacManus MP, Hicks RJ, Matthews JP, McKenzie A, Rischin D, Salminen EK, et al. (2003) Positron emission tomography is superior to computed tomography scanning for response-assessment after radical radiotherapy or chemoradiotherapy in patients with non-small-cell lung cancer. J Clin Oncol 21(7):1285–1292

    Article  Google Scholar 

  61. Barthel H, Cleij MC, Collingridge DR, Hutchinson OC, Osman S, He Q, et al. (2003) 3′-Deoxy-3′-[18F]fluorothymidine as a new marker for monitoring tumor response to antiproliferative therapy in vivo with positron emission tomography. Cancer Res 63(13):3791–3798

    PubMed  CAS  Google Scholar 

  62. Shields A, Lawhorn-Crews J, Briston D, Douglas K, Mangner T, Muzik O (2005) The reproducibility of FLT PET in patients with untreated non-small cell lung cancer. J Nucl Med 46:426

    Google Scholar 

  63. 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

    PubMed  CAS  Google Scholar 

  64. Weber WA, Ziegler SI, Thodtmann R, Hanauske AR, Schwaiger M (1999) Reproducibility of metabolic measurements in malignant tumors using FDG-PET. J Nucl Med 40(11):1771–1777

    PubMed  CAS  Google Scholar 

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  1. Karmanos Cancer Institute, Department of Medicine, Wayne State University, 4100 John R Street 4HWCRC, Detroit, MI, 48201-2013, USA

    Anthony F. Shields

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Shields, A.F. Positron Emission Tomography Measurement of Tumor Metabolism and Growth: Its Expanding Role in Oncology. Mol Imaging Biol 8, 141–150 (2006). https://doi.org/10.1007/s11307-006-0039-2

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