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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-07-2006

Is 3′-deoxy-3′-¹⁸F-fluorothymidine a better marker for tumour response than ¹⁸F-fluorodeoxyglucose?

Authors: Sven N. Reske, Sandra Deisenhofer

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Special Issue 1/2006

Abstract

3′-Deoxy-3′-¹⁸F-fluorothymidine (FLT) was developed in 1998 by Shields and co-workers because monitoring of treatment response would be facilitated by imaging agents able to provide measures of tissue and tumour proliferation. Since then, FLT metabolism has been clarified in more detail in cell culture and experimental animal tumour models and also in clinical studies. Recently, FLT has increasingly been used for the assessment of response to anticancer treatment, mainly in tumour xenograft SCID mouse models; in contrast, clinical data are scarce. In this article we briefly summarise the intermediary metabolism of FLT and its application as an anticancer treatment response probe. The potential value and limitations of FLT as a highly promising proliferation imaging probe and its use for monitoring of treatment response are discussed.

Hricak H, Akin O, Bradbury MS, Lieberman L, Schwartz LH, Larson SM. Advanced imaging methods: functional and metabolic imaging. In: DeVita VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. 7 ed. Philadelphia: Lippincott Williams & Wilkins; 2005. p. 589–720

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;92:205–16CrossRefPubMed

Reske SN, Kotzerke J. FDG-PET for clinical use. Results of the 3rd German Interdisciplinary Consensus Conference, “Onko-PET III”, 21 July and 19 September 2000. Eur J Nucl Med 2001;28:1707–23PubMedCrossRef

Gambhir SS. Molecular imaging of cancer with positron emission tomography. Nat Rev Cancer 2002;2:683–93CrossRefPubMed

Phelps ME. Positron emission tomography provides molecular imaging of biological processes. Proc Natl Acad Sci U S A 2000;97:9226–33PubMedCrossRef

Jerusalem G, Beguin Y, Fassotte MF, Belhocine T, Hustinx R, Rigo P, et al. Early detection of relapse by whole-body positron emission tomography in the follow-up of patients with Hodgkin’s disease. Ann Oncol 2003;14:123–30CrossRefPubMed

Weber WA, Ott K. Imaging of esophageal and gastric cancer. Semin Oncol 2004;31:530–41CrossRefPubMed

Juweid ME, Cheson BD. Positron-emission tomography and assessment of cancer therapy. N Engl J Med 2006;354:496–507CrossRefPubMed

Shields AF, Mankoff D, Graham MM, Zheng M, Kozawa SM, Link JM, et al. Analysis of 2-carbon-11-thymidine blood metabolites in PET imaging. J Nucl Med 1996;37:290–6PubMed

10.

Tjuvajev JG, Macapinlac 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;35:1407–17PubMed

11.

Blasberg RG, Roelcke U, Weinreich R, Beattie B, von Ammon K, Yonekawa Y, et al. Imaging brain tumor proliferative activity with [¹²⁴I]iododeoxyuridine. Cancer Res 2000;60:624–35PubMed

12.

Shields AF, Grierson JR, Dohmen BM, Machulla HJ, Stayanoff JC, Lawhorn-Crews JM, et al. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med 1998;4:1334–6CrossRefPubMed

13.

Plagemann PG, Richey DP, Zylka JM, Erbe J. Thymidine transport by Novikoff rat hepatoma cells synchronized by double hydroxyurea treatment. Exp Cell Res 1974;83:303–10CrossRefPubMed

14.

Hopwood LE, Dewey WC, Hejny W. Transport of thymidine during the cell cycle in mitotically synchronized CHO cells. Exp Cell Res 1975;96:425–9CrossRefPubMed

15.

Munch-Petersen B, Cloos L, Jensen HK, Tyrsted G. Human thymidine kinase 1. Regulation in normal and malignant cells. Adv Enzyme Regul 1995;35:69–89CrossRefPubMed

16.

Sherley JL, Kelly TJ. Regulation of human thymidine kinase during the cell cycle. J Biol Chem 1988;263:8350–8PubMed

17.

Eriksson S, Munch-Petersen B, Johansson K, Eklund H. Structure and function of cellular deoxyribonucleoside kinases. Cell Mol Life Sci 2002;59:1327–46CrossRefPubMed

18.

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;266:9032–8PubMed

19.

Wang J, Eriksson S. Phosphorylation of the anti-hepatitis B nucleoside analog 1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)-5-Iodouracil (FIAU) by human cytosolic and mitochondrial thymidine kinase and implications for cytotoxity. Antimicrob Agents Chemother 1996;40:1555–7PubMed

20.

Kornberg A, Baker TA. Biosynthesis in DNA precursors. DNA replication. 2nd ed. New York: W.H. Freeman; 1992. p. 53–100

21.

Skladanowski AC, Hoffmann C, Krass J, Jastorff B, Makarewicz W. Structure-activity relationship of cytoplasmic 5′-nucleotidase substrate sites. Biochem J 1996;314 Pt 3:1001–7PubMed

22.

Garvey EP, Lowen GT, Almond MR. Nucleotide and nucleoside analogues as inhibitors of cytosolic 5′-nucleotidase I from heart. Biochemistry 1998;37:9043–51CrossRefPubMed

23.

Gazziola C, Ferraro P, Moras M, Reichard P, Bianchi V. Cytosolic high K(m) 5′-nucleotidase and 5′(3′)-deoxyribonucleotidase in substrate cycles involved in nucleotide metabolism. J Biol Chem 2001;276:6185–90CrossRefPubMed

24.

Mansson E, Flordal E, Liliemark J, Spasokoukotskaja T, Elford H, Lagercrantz S, et al. Down-regulation of deoxycytidine kinase in human leukemic cell lines resistant to cladribine and clofarabine and increased ribonucleotide reductase activity contributes to fludarabine resistance. Biochem Pharmacol 2003;65:237–47CrossRefPubMed

25.

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;31:829–37CrossRefPubMed

26.

Kong XB, Zhu QY, Vidal PM, Watanabe KA, Polsky B, Armstrong D, et al. Comparisons of anti-human immunodeficiency virus activities, cellular transport, and plasma and intracellular pharmacokinetics of 3′-fluoro-3′-deoxythymidine and 3′-azido-3′-deoxythymidine. Antimicrob Agents Chemother 1992;36:808–18PubMed

27.

Sundseth R, Joyner S, Moore J, Dornsife R, Dev I. The anti-human immunodeficiency virus agent 3′-fluorothymidine induces DNA damage and apoptosis in human lymphoblastoid cells. Antimicrob Agents Chemother 1996;40:331–5PubMed

28.

Langen P, Etzold G, Hintsche R, Kowollik G. 3′-Deoxy-3′-fluorothymidine, a new selective inhibitor of DNA-synthesis. Acta Biol Med Ger 1969;23:759–66PubMed

29.

Matthes E, Lehmann C, Scholz D, Rosenthal HA, Langen P. Phosphorylation, anti-HIV activity and cytotoxicity of 3′-fluorothymidine. Biochem Biophys Res Commun 1988;153:825–31CrossRefPubMed

30.

Stryer L. Biochemistry. 4 ed. New York: W.H. Freeman; 1995

31.

Van Rompay AR, Johansson M, Karlsson A. Phosphorylation of nucleosides and nucleoside analogs by mammalian nucleoside monophosphate kinases. Pharmacol Ther 2000;87:189–98CrossRefPubMed

32.

Caligo MA, Cipollini G, Fiore L, Calvo S, Basolo F, Collecchi P, et al. NM23 gene expression correlates with cell growth rate and S-phase. Int J Cancer 1995;60:837–42PubMedCrossRef

33.

Lacombe M-L, Milon L, Munier A. The human Nm23/nucleoside diphosphate kinases. J Bioenerg Biomembr 2000;32:247–58CrossRefPubMed

34.

Been LB, Suurmeijer AJH, Cobben DCP, Jager PL, Hoekstra HJ, Elsinga PH. [¹⁸F]FLT-PET in oncology: current status and opportunities. Eur J Nucl Med Mol Imaging 2004;31:1659–72CrossRefPubMed

35.

Dittmann H, Dohmen BM, Kehlbach R, Bartusek G, Pritzkow M, Sarbia M, et al. Early changes in [¹⁸F]FLT uptake after chemotherapy: an experimental study. Eur J Nucl Med Mol Imaging 2002;29:1462–9CrossRefPubMed

36.

Beets G, Penninckx F, Schiepers C, Filez L, Mortelmans L, Kerremans R, et al. Clinical value of whole-body positron emission tomography with [¹⁸F]fluorodeoxyglucose in recurrent colorectal cancer. Br J Surg 1994;81:1666–70PubMedCrossRef

37.

Buck AK, Halter G, Schirrmeister H, Kotzerke J, Wurziger I, Glatting G, et al. Imaging proliferation in lung tumors with PET:¹⁸F-FLT versus¹⁸F-FDG. J Nucl Med 2003;44:1426–31PubMed

38.

Vesselle H, Grierson J, Muzi M, Pugsley JM, Schmidt RA, Rabinowitz P, et al. In vivo validation of 3′deoxy-3-[¹⁸F]fluorothymidine ([¹⁸F]FLT) as a proliferation imaging tracer in humans: correlation of [¹⁸F]FLT uptake by positron emission tomography with Ki-67 immunohistochemistry and flow cytometry in human lung tumors. Clin Cancer Res 2002;8:3315–23PubMed

39.

Cobben DC, Elsinga PH, Hoekstra HJ, Suurmeijer AJ, Vaalburg W, Maas B, et al. Is¹⁸F-3′-fluoro-3′-deoxy-L-thymidine useful for the staging and restaging of non-small cell lung cancer? J Nucl Med 2004;45:1677–82PubMed

40.

Cobben DC, Laan B, Maas B, Vaalburg W, Suurmeijer AJ, Hoekstra HJ, et al.¹⁸F-FLT PET for visualization of laryngeal cancer: comparison with¹⁸F-FDG PET. J Nucl Med 2004;45:226–31PubMed

41.

van Westreenen HL, Cobben DC, Jager PL, van Dullemen HM, Wesseling J, Elsinga PH, et al. Comparison of¹⁸F-FLT PET and¹⁸F-FDG PET in esophageal cancer. J Nucl Med 2005;46:400–4PubMed

42.

Buck AK, Schirrmeister H, Hetzel M, Von Der Heide M, Halter G, Glatting G, et al. 3-deoxy-3-[¹⁸F]fluorothymidine-positron emission tomography for noninvasive assessment of proliferation in pulmonary nodules. Cancer Res 2002;62:3331–4PubMed

43.

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;46:274–82PubMed

44.

Yap CS, Czernin J, Fishbein MC, Cameron RB, Schiepers C, Phelps ME, et al. Evaluation of thoracic tumors with 18F-fluorothymidine and¹⁸F-fluorodeoxyglucose-positron emission tomography. Chest 2006;129:393–401CrossRefPubMed

45.

Chen W, Cloughesy T, Kamdar N, Satyamurthy N, Bergsneider M, Liau L, et al. Imaging proliferation in brain tumors with¹⁸F-FLT PET: comparison with¹⁸F-FDG. J Nucl Med 2005;46:945–52PubMed

46.

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;31:720–4CrossRefPubMed

47.

Pio BS, Park CK, Pietras R, Hsueh WA, Satyamurthy N, Pegram MD, et al. Usefulness of 3′-[F-18]fluoro-3′-deoxythymidine with positron emission tomography in predicting breast cancer response to therapy. Mol Imaging Biol 2006;8:36–42CrossRefPubMed

48.

Jakob C, Liersch T, Meyer W, Baretton GB, Hausler P, Schwabe W, et al. Immunohistochemical analysis of thymidylate synthase, thymidine phosphorylase, and dihydropyrimidine dehydrogenase in rectal cancer (cUICC II/III): correlation with histopathologic tumor regression after 5-fluorouracil-based long-term neoadjuvant chemoradiotherapy. Am J Surg Pathol 2005;29:1304–9CrossRefPubMed

49.

Ma T, Zhu ZG, Ji YB, Zhang Y, Yu YY, Liu BY, et al. Correlation of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase with sensitivity of gastrointestinal cancer cells to 5-fluorouracil and 5-fluoro-2′-deoxyuridine. World J Gastroenterol 2004;10:172–6PubMed

50.

Rosenwald A, Staudt LM. Clinical translation of gene expression profiling in lymphomas and leukemias. Semin Oncol 2002;29:258–63CrossRefPubMed

51.

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;46:114–20PubMed

52.

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;45:1754–8PubMed

53.

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;65:4202–10CrossRefPubMed

54.

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;63:3791–8PubMed

55.

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 2005;45:519–25

Title: Is 3′-deoxy-3′-18F-fluorothymidine a better marker for tumour response than 18F-fluorodeoxyglucose?
Authors: Sven N. Reske
Sandra Deisenhofer
Publication date: 01-07-2006
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue Special Issue 1/2006
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-006-0134-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Is 3′-deoxy-3′-¹⁸F-fluorothymidine a better marker for tumour response than ¹⁸F-fluorodeoxyglucose?

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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