Skip to main content
SpringerLink
Log in

Measurement of Tumor Proliferation with Positron Emission Tomography and Treatment Response

  • Chapter
In Vivo Imaging of Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

  • 617 Accesses

Abstract

While the ultimate goal of cancer treatment is to eliminate all evidence of the tumor’s presence, the more immediate goal of treatment with chemotherapy, radiation, and biological agents is to decrease the tumor’s ability to replicate and increase the death rate of cancer cells. This basis has inspired researchers to design and develop imaging approaches to assess tumor proliferation and, more importantly, a tumor’s response to new treatments. Such approaches, while still in development, may complement the routine imaging of tumor size now done as part of standard clinical care. In general, successful therapy should lead to declines in the size of tumors as reflected by techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) (1,2). While anatomic imaging is relatively straightforward and readily available, it has a number of limitation. First, it measures the size of the mass, but does not determine the cellularity or growth rate of the tumor. Second, after treatment, the tumor may be left with a fibrotic mass that can persist even after successful treatment. While eventually a mass may decline in size after therapy, this can take many weeks to months for the cells to lyse and finally to be absorbed. Finally, when therapy is unsuccessful, it may take months for the failure of treatment to become apparent, since tumors may grow very slowly. In fact, the doubling time of most tumors is generally from 1 to 3 months (3). It is for these reasons that imaging cell proliferation is attractive to assess treatment response and for potential use to steer or change a course of therapy. This approach to positron emission tomography (PET) imaging may also complement imaging other aspects of tumor metabolism, such as energetics, protein and membrane synthesis, and apoptosis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

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

    Article  PubMed  CAS  Google Scholar 

  2. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. 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 2000;92(3):205–216.

    Article  PubMed  CAS  Google Scholar 

  3. Skehan P. On the normality of growth dynamics of neoplasms in vivo: A data base analysis. Growth 1986;50(4):496–515.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  5. Shields AF, Mankoff DA, Link JM, Graham MM, Eary JF, Kozawa M, et al. [11C]Thymidine and FDG to measure therapy response. J Nucl Med 1998;39:1757–1762.

    PubMed  CAS  Google Scholar 

  6. Mossman PB, Young LL, 3rd. Testing for degrees of color blindness. Occup Health Saf 1983;52(8):49–53, 55.

    PubMed  CAS  Google Scholar 

  7. Tannock I. Cell kinetics and chemotherapy: A critical review. Cancer Treat Rep 1978;62(8):1117–1133.

    PubMed  CAS  Google Scholar 

  8. Cleaver JE. Thymidine metabolism and cell kinetics. Frontiers Biol 1967;6:43–100.

    Google Scholar 

  9. Reid BJ, Haggitt RC, Rubin CE, Rabinovitch PS. Barrett’s esophagus. Correlation between flow cytometry and histology in detection of patients at risk for adenocarcinoma. Gastroenterology 1987;93(1):1–11.

    PubMed  CAS  Google Scholar 

  10. Livingston RB, Sulkes A, Thirwell MP, Murphy WK, Hart JS. Cell kinetic parameters: Correlation with clinical response. In: Drewinko B, Humphrey RM, eds. Growth Kinetics and Biochemical Regulation of Normal and Malignant Cells. Baltimore: Williams & Wilkins, 1977:767–785.

    Google Scholar 

  11. Wilson GD. Assessment of human tumour proliferation using bromodeoxyuridine-current status. Acta Oncol 1991;30(8):903–910.

    Article  PubMed  CAS  Google Scholar 

  12. Gardelle O, Roelcke U, Vontobel P, Crompton NE, Guenther I, Blauenstein P, et al. [76Br]Bromodeoxyuridine PET in tumor-bearing animals. Nucl Med Biol 2001;28(1):51–57.

    Article  PubMed  CAS  Google Scholar 

  13. Ryser JE, Blauenstein P, Remy N, Weinreich R, Hasler PH, Novak-Hofer I, et al. [76Br]Bromodeoxyuridine, a potential tracer for the measurement of cell proliferation by positron emission tomography, in vitro and in vivo studies in mice. Nucl Med Biol 1999;26(6):673–679.

    Article  PubMed  CAS  Google Scholar 

  14. Scholzen T, Gerdes J. The Ki-67 protein: From the known and the unknown. J Cell Physiol 2000;182(3):311–322.

    Article  PubMed  CAS  Google Scholar 

  15. Pugsley JM, Schmidt RA, Vesselle H. The Ki-67 index and survival in non-small cell lung cancer: A review and relevance to positron emission tomography. Cancer J 2002;8(3):222–233.

    Article  PubMed  Google Scholar 

  16. Chung JK, Lee YJ, Kim SK, Jeong JM, Lee DS, Lee MC. Comparison of [18F]fluorodeoxyglucose uptake with glucose transporter-1 expression and proliferation rate in human glioma and non-smallcell lung cancer. Nucl Med Commun 2004;25(1):11–17.

    Article  PubMed  CAS  Google Scholar 

  17. Kim S, Chung JK, Im SH, Jeong JM, Lee DS, Kim DG, et al. 11C-Methionine PET as a prognostic marker in patients with glioma: Comparison with 18F-FDG PET. Eur J Nucl Med Mol Imaging 2005;32(1):52–59.

    Article  PubMed  CAS  Google Scholar 

  18. Utriainen M, Metsahonkala L, Salmi TT, Utriainen T, Kalimo H, Pihko H, et al. Metabolic characterization of childhood brain tumors: Comparison of 18F-fluorodeoxyglucose and 11C-methionine positron emission tomography. Cancer 2002;95(6):1376–1386.

    Article  PubMed  Google Scholar 

  19. Higashi K, Ueda Y, Yagishita M, Arisaka Y, Sakurai A, Oguchi M, et al. FDG PET measurement of the proliferative potential of non-small cell lung cancer. J Nucl Med 2000;41(1):85–92.

    PubMed  CAS  Google Scholar 

  20. Brown RS, Leung JY, Kison PV, Zasadny KR, Flint A, Wahl RL. Glucose transporters and FDG uptake in untreated primary human non-small cell lung cancer. J Nucl Med 1999;40(4):556–565.

    PubMed  CAS  Google Scholar 

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

    Google Scholar 

  22. Larson SM, Weiden PL, Grunbaum Z, Rasey JS, Kaplan HG, Graham MM, et al. Positron imaging feasibility studies. I: Characteristics of [3H]thymidine uptake in rodent and canine neoplasms: Concise communication. J Nucl Med 1981;22(10):869–874.

    PubMed  CAS  Google Scholar 

  23. Shields AF, Larson SM, Grunbaum Z, Graham MM. Short-term thymidine uptake in normal and neoplastic tissues: Studies for PET. J Nucl Med 1984;25:759–764.

    PubMed  CAS  Google Scholar 

  24. Christman D, Crawford EJ, Friedkin M, Wolf AP. Detection of DNA synthesis in intact organisms with positron-emitting (methyl-11C)thymidine. Proc Natl Acad Sci USA 1972;69(4):988–992.

    Article  PubMed  CAS  Google Scholar 

  25. Sundoro-Wu BM, Schmall B, Conti PS, Dahl JR, Drumm P, Jacobsen JK. Selective alkylation of pyrimidyl-dianions: Synthesis and purification of 11C labeled thymidine for tumor visualization using positron emission tomography. Int J Appl Radiat Isotopes 1984;35:705–708.

    Article  CAS  Google Scholar 

  26. Vander Borght T, Labar D, Pauwels S, Lambotte L. Production of [2-11C]Thymidine for quantification of cellular proliferation with PET. Appl Radiat Isotopes 1991;42:103–104.

    Article  CAS  Google Scholar 

  27. Becherer A, Karanikas G, Szabo M, Zettinig G, Asenbaum S, Marosi C, et al. Brain tumour imaging with PET: A comparison between [18F]fluorodopa and [11C]methionine. Eur J Nucl Med Mol Imaging 2003;30(11):1561–1567.

    Article  PubMed  CAS  Google Scholar 

  28. Shields AF, Lim K, Grierson J, Link J, Krohn KA. Utilization of labeled thymidine in DNA synthesis: Studies for PET. J Nucl Med 1990;31(3):337–342.

    PubMed  CAS  Google Scholar 

  29. Shields AF, Mankoff D, Graham MM, Zheng M, Kozawa SM, Link J, et al. Analysis of [2-11C]thymidine blood metabolites for imaging with PET. J Nucl Med 1996;37:290–296.

    PubMed  CAS  Google Scholar 

  30. Shields AF, Graham MM, Kozawa SM, Kozell LB, Link JM, Swenson ER, et al. Contribution of labeled carbon dioxide to PET imaging of carbon-11-labeled compounds. J Nucl Med 1992;33(4):581–584.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  32. Mankoff DA, Shields AF, Graham MM, Link JM, Krohn KA. A graphical analysis method for estimating blood-to-tissue transfer constants for tracers with labeled metabolites. J Nucl Med 1996;37(12):2049–2057.

    PubMed  CAS  Google Scholar 

  33. Wells P, Gunn RN, Alison M, Steel C, Golding M, Ranicar AS, et al. Assessment of proliferation in vivo using 2-[(11)C]thymidine positron emission tomography in advanced intra-abdominal malignancies. Cancer Res 2002;62(20):5698–5702.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  35. Ritzel MW, Yao SY, Huang MY, Elliott JF, Cass CE, Young JD. Molecular cloning and functional expression of cDNAs encoding a human Na+-nucleoside cotransporter (hCNT1). Am J Physiol 1997;272(2 Pt 1):C707–C714.

    PubMed  CAS  Google Scholar 

  36. Baldwin SA, Beal PR, Yao SY, King AE, Cass CE, Young JD. The equilibrative nucleoside transporter family, SLC29. Pflugers Arch 2004;447(5):735–743.

    Article  PubMed  CAS  Google Scholar 

  37. Sherley JL, Kelly TJ. Regulation of human thymidine kinase during the cell cycle. J Biol Chem 1988;263(17):8350–8358.

    PubMed  CAS  Google Scholar 

  38. Shields AF, Coonrod DV, Quackenbush RC, Crowley JJ. Cellular sources of thymidine nucleotides: Studies for PET. J Nucl Med 1987;28:1435–1440.

    PubMed  CAS  Google Scholar 

  39. Mankoff D, Shields A, Link J, Graham M, Muzi M, Peterson L, et al. Kinetic analysis of 2-[C-11]-thymidine PET imaging studies: Validation studies. J Nucl Med 1999;40(4):614–624.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  42. van Eijkeren ME, De Schryver A, Goethals P, Poupeye E, Schelstraete K, Lemahieu I, et al. Measurement of short-term 11C-thymidine activity in human head and neck tumours using positron emission tomography (PET). Acta Oncol 1992;31(5):539–543.

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  44. Wells P, Gunn RN, Steel C, Ranicar AS, Brady F, Osman S, et al. 2-[11C]Thymidine positron emission tomography reproducibility in humans. Clin Cancer Res 2005;11(12):4341–4347.

    Article  PubMed  CAS  Google Scholar 

  45. De Reuck J, Santens P, Goethals P, Strijckmans K, Lemahieu I, Boon P, et al. [Methyl-11C]thymidine positron emission tomography in tumoral and non-tumoral cerebral lesions. Acta Neurol Belg 1999;99(2):118–125.

    PubMed  Google Scholar 

  46. Propper DJ, McDonald AC, Man A, Thavasu P, Balkwill F, Braybrooke JP, et al. Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C. J Clin Oncol 2001;19(5):1485–1492.

    PubMed  CAS  Google Scholar 

  47. Wells P, West C, Jones T, Harris A, Price P. Measuring tumor pharmacodynamic response using PET proliferation probes: The case for 2-[(11)C]-thymidine. Biochim Biophys Acta 2004;1705(2):91–102.

    PubMed  CAS  Google Scholar 

  48. Wells P, Aboagye E, Gunn RN, Osman S, Boddy AV, Taylor GA, et al. 2-[11C]Thymidine positron emission tomography as an indicator of thymidylate synthase inhibition in patients treated with AG337. J Natl Cancer Inst 2003;95(9):675–682.

    Article  PubMed  CAS  Google Scholar 

  49. Heidelberger C, Chaudhuri NK, Danneberg P, et al. Fluorinated pyrimidines, a new class of tumorinhibitory compounds. Nature 1957;179:663.

    Article  PubMed  CAS  Google Scholar 

  50. Eidinoff ML, Cheong L, Gurpide EG, Benua RS, Ellison RR. Incorporation of 5-iodouracil labelled with iodine-131 into the deoxyribonucleic acid of human leukaemic leucocytes following in vivo administration of 5-iododeoxyuridine labelled with iodine-131. Nature 1959;183(4676):1686–1687.

    Article  PubMed  CAS  Google Scholar 

  51. Philip PA, Bagshawe KD, Searle F, Green AJ, Begent RH, Newlands ES, et al. In vivo uptake of 131I-5-iodo-2-deoxyuridine by malignant tumours in man. Br J Cancer 1991;63(1):134–135.

    PubMed  CAS  Google Scholar 

  52. Tjuvajev JG, Macapinilac HA, Daghighian F, Scott AM, Ginos JZ, Finn RD, et al. Imaging of brain tumor proliferative activity with iodine-131-iododeoxyuridine. J Nucl Med 1994;35(9):1407–1417.

    PubMed  CAS  Google Scholar 

  53. Kriss JP, Maruyama Y, Tung LA, Bond SB, Revesz L. The fate of 5-bromodeoxycytodine and 5-iododeoxyruridine in man. Cancer Res 1963;23:260–273.

    PubMed  CAS  Google Scholar 

  54. Bergstrom M, Lu L, Fasth KJ, Wu F, Bergstrom-Pettermann E, Tolmachev V, et al. In vitro and animal validation of bromine-76-bromodeoxyuridine as a proliferation marker. J Nucl Med 1998;39(7):1273–1279.

    PubMed  CAS  Google Scholar 

  55. Gudjonsson O, Bergstrom M, Kristjansson S, Wu F, Nyberg G, Fasth KJ, et al. Analysis of 76Br-BrdU in DNA of brain tumors after a PET study does not support its use as a proliferation marker. Nucl Med Biol 2001;28(1):59–65.

    Article  Google Scholar 

  56. Fowler JS, Finn RD, Lambrecht RM, Wolf AP. The synthesis of 18F-5-fluorouracil. VII. J Nucl Med 1973;14:63–64.

    PubMed  CAS  Google Scholar 

  57. Dimitrakopoulou-Strauss A, Strauss LG, Schlag P, Hohenberger P, Mohler M, Oberdorfer F, et al. Fluorine-18-fluorouracil to predict therapy response in liver metastases from colorectal carcinoma. J Nucl Med 1998;39(7):1197–1202.

    PubMed  CAS  Google Scholar 

  58. Abe Y, Fukuda H, Ishiwata K, Yoshioka S, Yamada K, Endo S, et al. Studies on 18F-labeled pyrimidines. Tumor uptakes of 18F-5-fluorouracil, 18F-5-fluorouridine, and 18F-5-fluoro-2′-deoxyuridine in animals. Eur J Nucl Med 1983;8:258–261.

    Article  PubMed  CAS  Google Scholar 

  59. Shani J, Wolf W, Schlesinger T, Atkins HL, Bradley-Moore PR, Casella V, et al. Distribution of 18F-5-fluorouracil in tumor-bearing mice and rats. Int J Nucl Med Biol 1978;5(1):19–28.

    Article  PubMed  CAS  Google Scholar 

  60. Crawford EJ, Friedkin M, Wolf AP, Fowler JS, Gallagher BM, Lambrecht RM, et al. 18F-5-Fluorouridine, a new probe for measuring the proliferation of tissue in vivo. Adv Enzyme Regul 1982;20:3–22.

    Article  PubMed  Google Scholar 

  61. Seitz U, Wagner M, Vogg AT, Glatting G, Neumaier B, Greten FR, et al. In vivo evaluation of 5-[(18)F]fluoro-2′-deoxyuridine as tracer for positron emission tomography in a murine pancreatic cancer model. Cancer Res 2001;61(10):3853–3857.

    PubMed  CAS  Google Scholar 

  62. Buchmann I, Vogg AT, Glatting G, Schultheiss S, Moller P, Leithauser F, et al. [18F]5-Fluoro-2-deoxyuridine-PET for imaging of malignant tumors and for measuring tissue proliferation. Cancer Biother Radiopharm 2003;18(3):327–337.

    Article  PubMed  CAS  Google Scholar 

  63. Conti P, Alauddin M, Fissekis J, Schmall B, Watanabe K. 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 1995;22(6):783–789.

    Article  PubMed  CAS  Google Scholar 

  64. Lu L, Bergstrom M, Fasth KJ, Langstrom B. Synthesis of [76Br]bromofluorodeoxyuridine and its validation with regard to uptake, DNA incorporation, and excretion modulation in rats. J Nucl Med 2000;41(10):1746–1752.

    PubMed  CAS  Google Scholar 

  65. Nimmagadda S, Mangner TJ, Sun H, Klecker RW, Jr., Muzik O, Lawhorn-Crews JM, et al. Biodistribution and radiation dosimetry estimates of 1-(2′-deoxy-2′-(18)F-fluoro-1-beta-D-arabinofuranosyl)-5-bromouracil: PET imaging studies in dogs. J Nucl Med 2005;46(11):1916–1922

    PubMed  CAS  Google Scholar 

  66. Shields A, Grierson J, Dohmen B, Machulla H-J, Stayanoff J, Lawhorn-Crews J, et al. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nature Med 1998;4:1334–1336.

    Article  PubMed  CAS  Google Scholar 

  67. Shields AF, Grierson JR, Kozawa SM, Zheng M. Development of labeled thymidine analogs for imaging tumor proliferation. Nuclear Med Biol 1996;23(1):17–22.

    Article  CAS  Google Scholar 

  68. Mangner T, Klecker R, Anderson L, Shields A. Synthesis of 2′-[18F]fluoro-2′-deoxy-β-Darabinofuranosyl nucleotides, [18F]FAU, [18F]FMAU, [18F]FBAU and [18F]FIAU, as potential PET agents for imaging cellular proliferation. Nucl Med Biol 2003 (30):215–22

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  70. Matthes E, Lehmann C, Scholz D, Rosenthal HA, Langen P. Phosphorylation, anti-HIV activity and cytotoxicity of 3′-fluorothymidine. Biochem Biophys Res Commun 1988;153(2):825–831.

    Article  PubMed  CAS  Google Scholar 

  71. Lundgren B, Bottiger D, Ljungdahl-Stahle E, Norrby E, Stahle L, Wahren B, et al. Antiviral effects of 3′-fluorothymidine and 3′-azidothymidine in cynomolgus monkeys infected with simian immunodeficiency virus. J Acquir Immune Defic Syndr 1991;4(5):489–498

    PubMed  CAS  Google Scholar 

  72. Flexner C, van der Horst C, Jacobson MA, Powderly W, Duncanson F, Ganes D, et al. Relationship between plasma concentrations of 3′-deoxy-3′-fluorothymidine (alovudine) and antiretroviral activity in two concentration-controlled trials. J Infect Dis 1994;170(6):1394–1403

    PubMed  CAS  Google Scholar 

  73. Grierson J, Shields A. A strategy for the labeling of [F-18]-3′-deoxy-3′-fluorothymidine: [F-18]FLT. J Labelled Comp Radiopharm 1995;37:606–607

    Google Scholar 

  74. Grierson JR, Shields AF. An improved synthesis of [18F]FLT. J Labelled Comp Radiopharm 1999;42(Suppl 1):S525–S526.

    Google Scholar 

  75. Grierson JR, Shields AF. Radiosynthesis of 3′-deoxy-3′-[(18)F]fluorothymidine: [(18)F]FLT for imaging of cellular proliferation in vivo. Nucl Med Biol 2000;27(2):143–156

    Article  PubMed  CAS  Google Scholar 

  76. Machulla H-J, Blocher A, Kuntzsch M, Wei R, Grierson J. Simplified labeling approach for synthesizing 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT). J Radioanalyt Nucl Chem 2000;243:843–846

    Article  CAS  Google Scholar 

  77. Muzi M, Vesselle H, Grierson JR, Mankoff DA, Schmidt RA, Peterson L, et al. Kinetic analysis of 3′-deoxy-3′-fluorothymidine PET studies: Validation studies in patients with lung cancer. J Nucl Med 2005;46(2):274–282

    PubMed  CAS  Google Scholar 

  78. Shields AF, Briston DA, Chandupatla S, Douglas KA, Lawhorn-Crews J, Collins JM, et al. A simplified analysis of [18F]3′-deoxy-3′-fluorothymidine metabolism and retention. Eur J Nucl Med Mol Imaging 2005;32(11):1269–1275

    PubMed  CAS  Google Scholar 

  79. Wagner M, Seitz U, Buck A, Neumaier B, Schultheiss S, Bangerter M, et al. 3′-[18F]Fluoro-3′-deoxythymidine ([18F]-FLT) as positron emission tomography tracer for imaging proliferation in a murine B-cell lymphoma model and in the human disease. Cancer Res 2003;63(10):2681–2687

    PubMed  CAS  Google Scholar 

  80. Grierson JR, Schwartz JL, Muzi M, Jordan R, Krohn KA. Metabolism of 3′-deoxy-3′-[F-18]fluorothymidine in proliferating A549 cells: Validations for positron emission tomography. Nucl Med Biol 2004;31(7):829–837

    Article  PubMed  CAS  Google Scholar 

  81. Seitz U, Wagner M, Neumaier B, Wawra E, Glatting G, Leder G, et al. Evaluation of pyrimidine metabolising enzymes and in vitro uptake of 3′-[(18)F]fluoro-3′-deoxythymidine ([(18)F]FLT) in pancreatic cancer cell lines. Eur J Nucl Med Mol Imaging 2002;29(9):1174–1181

    Article  PubMed  CAS  Google Scholar 

  82. Munch-Petersen B, Cloos L, Tyrsted G, Eriksson S. Diverging substrate specificity of pure human thymidine kinases 1 and 2 against antiviral dideoxynucleosides. J Biol Chem 1991;266(14):9032–9038.

    PubMed  CAS  Google Scholar 

  83. Jansson O, Bohman C, Munch-Petersen B, Eriksson S. Mammalian thymidine kinase 2: Direct photoaffinity labeling with [32P]dTTP of the enzyme from spleen, liver, heart and brain. Eur J Biochem 1992;206:485–490.

    Article  PubMed  CAS  Google Scholar 

  84. Shields A, Grierson JR, Muzik O, Stayanoff JC, Lawhorn-Crews J, Obradovich JE, et al. Kinetics of 3′-deoxy-3′-[F-18]fluorothymidine uptake and retention in dogs. Mol Imaging Biol 2002:83–89

    Google Scholar 

  85. Visvikis D, Francis D, Mulligan R, Costa DC, Croasdale I, Luthra SK, et al. Comparison of methodologies for the in vivo assessment of 18FLT utilisation in colorectal cancer. Eur J Nucl Med Mol Imaging 2004;31(2):169–178.

    Article  PubMed  CAS  Google Scholar 

  86. Muzi M, Mankoff DA, Grierson JR, Wells JM, Vesselle H, Krohn KA. Kinetic modeling of 3′-deoxy-3′-fluorothymidine in somatic tumors: Mathematical studies. J Nucl Med 2005;46(2):371–380

    PubMed  CAS  Google Scholar 

  87. Kenny LM, Vigushin DM, Al-Nahhas A, Osman S, Luthra SK, Shousha S, et al. Quantification of cellular proliferation in tumor and normal tissues of patients with breast cancer by [18F]fluorothymidinepositron emission tomography imaging: Evaluation of analytical methods. Cancer Res 2005;65(21):10104–10112.

    Article  PubMed  CAS  Google Scholar 

  88. Gjedde A. Calculation of cerebral glucose phosphorylation from brain uptake of glucose analogs in vivo: A re-examination. Brain Res Rev 1982;4:237–274.

    Article  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  90. Minn H, Zasadny KR, Quint LE, Wahl RL. Lung cancer: Reproducibility of quantitative measurements for evaluating 2-[F-18]-fluoro-2-deoxy-D-glucose uptake at PET. Radiology 1995;196(1):167–173.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    Google Scholar 

  93. Tseng JR, Dandekar M, Subbarayan M, Cheng Z, Park JM, Louie S, et al. Reproducibility of 3′-deoxy-3′-(18)F-fluorothymidine microPET studies in tumor xenografts in mice. J Nucl Med 2005;46(11):1851–1857

    PubMed  CAS  Google Scholar 

  94. Mankoff DA, Shields AF, Krohn KA. PET imaging of cellular proliferation. Radiol Clin North Am 2005;43(1):153–167.

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  96. Cobben DC, Elsinga PH, Suurmeijer AJ, Vaalburg W, Maas B, Jager PL, et al. Detection and grading of soft tissue sarcomas of the extremities with (18)F-3′-fluoro-3′-deoxy-L-thymidine. Clin Cancer Res 2004;10(5):1685–1690

    Article  PubMed  CAS  Google Scholar 

  97. Francis DL, Freeman A, Visvikis D, Costa DC, Luthra SK, Novelli M, et al. In vivo imaging of cellular proliferation in colorectal cancer using positron emission tomography. Gut 2003;52(11):1602–1606.

    Article  PubMed  CAS  Google Scholar 

  98. Vesselle H, Grierson J, Muzi M, Pugsley JM, Schmidt RA, Rabinowitz P, et al. 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 2002;8(11):3315–3323

    PubMed  CAS  Google Scholar 

  99. Smyczek-Gargya B, Fersis N, Dittmann H, Vogel U, Reischl G, Machulla HJ, et al. PET with [18F]fluorothymidine for imaging of primary breast cancer: A pilot study. Eur J Nucl Med Mol Imaging 2004;31(5):720–724.

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  101. Dittmann H, Dohmen BM, Paulsen F, Eichhorn K, Eschmann SM, Horger M, et al. [18F]FLT PET for diagnosis and staging of thoracic tumours. Eur J Nucl Med Mol Imaging 2003;30(10):1407–1412.

    Article  PubMed  CAS  Google Scholar 

  102. Francis DL, Visvikis D, Costa DC, Arulampalam TH, Townsend C, Luthra SK, et al. 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 2003;30(7):988–994

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  104. Choi SJ, Kim JS, Kim JH, Oh SJ, Lee JG, Kim CJ, et al. [18F]3′-Deoxy-3′-fluorothymidine PET for the diagnosis and grading of brain tumors. Eur J Nucl Med Mol Imaging 2005;32(6):653–659

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  106. Oyama N, Ponde DE, Dence C, Kim J, Tai YC, Welch MJ. Monitoring of therapy in androgen-dependent prostate tumor model by measuring tumor proliferation. J Nucl Med 2004;45(3):519–525.

    PubMed  CAS  Google Scholar 

  107. Leyton J, Latigo JR, Perumal M, Dhaliwal H, He Q, Aboagye EO. Early detection of tumor response to chemotherapy by 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography: The effect of cisplatin on a fibrosarcoma tumor model in vivo. Cancer Res 2005;65(10):4202–4210

    Article  PubMed  CAS  Google Scholar 

  108. Sugiyama M, Sakahara H, Sato K, Harada N, Fukumoto D, Kakiuchi T, et al. Evaluation of 3′-deoxy-3′-18F-fluorothymidine for monitoring tumor response to radiotherapy and photodynamic therapy in mice. J Nucl Med 2004;45(10):1754–1758

    PubMed  CAS  Google Scholar 

  109. Waldherr C, Mellinghoff IK, Tran C, Halpern BS, Rozengurt N, Safaei A, et al. Monitoring antiproliferative responses to kinase inhibitor therapy in mice with 3′-deoxy-3′-18F-fluorothymidine PET. J Nucl Med 2005;46(1):114–120

    PubMed  CAS  Google Scholar 

  110. Dittmann H, Dohmen BM, Kehlbach R, Bartusek G, Pritzkow M, Sarbia M, et al. Early changes in [(18)F]FLT uptake after chemotherapy: An experimental study. Eur J Nucl Med Mol Imaging 2002;29(11):1462–1469.

    Article  PubMed  CAS  Google Scholar 

  111. Bading JR, Shahinian AH, Bathija P, Conti PS. Pharmacokinetics of the thymidine analog 2′-fluoro-5-[(14)C]-methyl-1-beta-D-arabinofuranosyluracil ([(14)C]FMAU) in rat prostate tumor cells. Nucl Med Biol 2000;27(4):361–368.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  113. Collins JM, Klecker RW, Katki AG. Suicide prodrugs activated by thymidylate synthase: Rationale for treatment and noninvasive imaging of tumors with deoxyuridine analogues. Clin Cancer Res 1999;5(8):1976–1981.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI

    Anthony F. Shields MD, PhD

Authors
  1. Anthony F. Shields MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI

    Anthony F. Shields

  2. Manchester Molecular Imaging Center Christie Hospital NHS Trust Academic Department of Radiation Oncology, The University of Manchester Wolfson Molecular Imaging Centre, Manchester, UK

    Pat Price

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Shields, A.F. (2007). Measurement of Tumor Proliferation with Positron Emission Tomography and Treatment Response. In: Shields, A.F., Price, P. (eds) In Vivo Imaging of Cancer Therapy. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-341-7_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-341-7_8

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-633-7

  • Online ISBN: 978-1-59745-341-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation