Imaging early changes in proliferation at 1 week post chemotherapy: a pilot study in breast cancer patients with 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography

  • Laura Kenny
  • R. Charles Coombes
  • David M. Vigushin
  • Adil Al-Nahhas
  • Sami Shousha
  • Eric O. AboagyeEmail author
Original Article



3′-Deoxy-3′-[18F]fluorothymidine positron emission tomography ([18F]FLT-PET) has been developed for imaging cell proliferation and findings correlate strongly with the Ki-67 labelling index in breast cancer. The aims of this pilot study were to define objective criteria for [18F]FLT response and to examine whether [18F]FLT-PET can be used to quantify early response of breast cancer to chemotherapy.


Seventeen discrete lesions in 13 patients with stage II–IV breast cancer were scanned prior to and at 1 week after treatment with combination 5-fluorouracil, epirubicin and cyclophosphamide (FEC) chemotherapy. The uptake at 90 min (SUV90) and irreversible trapping (K i) of [18F]FLT were calculated for each tumour. The reproducibility of [18F]FLT-PET was determined in nine discrete lesions from eight patients who were scanned twice before chemotherapy. Clinical response was assessed at 60 days after commencing FEC.


All tumours showed [18F]FLT uptake and this was reproducible in serial measurements (SD of mean % difference = 10.5% and 15.1%, for SUV90 and K i, respectively; test–retest correlation coefficient ≥0.97). Six patients had a significant clinical response (complete or partial) at day 60; these patients also had a significant reduction in [18F]FLT uptake at 1 week. Decreases in K i and SUV90 at 1 week discriminated between clinical response and stable disease (p = 0.022 for both parameters). In three patients with multiple lesions there was a mixed [18F]FLT response in primary tumours and metastases. [18F]FLT response generally preceded tumour size changes.


[18F]FLT-PET can detect changes in breast cancer proliferation at 1 week after FEC chemotherapy.


FLT PET Breast cancer Response 



This study was supported by the UK Medical Research Council (MRC), London, and we are grateful for this support. R.C.C.’s and E.O.A.’s research is also funded by CRUK.

We wish to express our gratitude to the patients, radiographers and staff at Hammersmith Imanet Ltd, without whom this study would not have been possible.


  1. 1.
    Surveillance E, End Results (SEER) Program ( SEER*Stat Database: Incidence-SEER 17 Regs Public-Use, Nov 2005 Sub (1973–2003 varying), National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2006, based on the November 2005 submission.
  2. 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;92:205–16.PubMedCrossRefGoogle Scholar
  3. 3.
    Korn EL, Arbuck SG, Pluda JM, Simon R, Kaplan RS, Christian MC. Clinical trial designs for cytostatic agents: are new approaches needed? J Clin Oncol 2001;19:265–72.PubMedGoogle Scholar
  4. 4.
    Dowsett M, Archer C, Assersohn L, Gregory RK, Ellis PA, Salter J, et al. Clinical studies of apoptosis and proliferation in breast cancer. Endocr Relat Cancer 1999;6:25–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Ellis MJ, Coop A, Singh B, Tao Y, Llombart-Cussac A, Janicke F, et al. Letrozole inhibits tumor proliferation more effectively than tamoxifen independent of HER1/2 expression status. Cancer Res 2003;63:6523–31.PubMedGoogle Scholar
  6. 6.
    Ellis MJ, Rosen E, Dressman H, Marks J. Neoadjuvant comparisons of aromatase inhibitors and tamoxifen: pretreatment determinants of response and on-treatment effect. J Steroid Biochem Mol Biol 2003;86:301–7.PubMedCrossRefGoogle Scholar
  7. 7.
    van Diest PJ, van der Wall E, Baak JP. Prognostic value of proliferation in invasive breast cancer: a review. J Clin Pathol 2004;57:675–81.PubMedCrossRefGoogle Scholar
  8. 8.
    Vincent-Salomon A, Rousseau A, Jouve M, Beuzeboc P, Sigal-Zafrani B, Freneaux P, et al. Proliferation markers predictive of the pathological response and disease outcome of patients with breast carcinomas treated by anthracycline-based preoperative chemotherapy. Eur J Cancer 2004;40:1502–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Wahl RL, Zasadny K, Helvie M, Hutchins GD, Weber B, Cody R. Metabolic monitoring of breast cancer chemohormonotherapy using positron emission tomography: initial evaluation. J Clin Oncol 1993;11:2101–11.PubMedGoogle Scholar
  10. 10.
    Weber WA, Ziegler SI, Thodtmann R, Hanauske AR, Schwaiger M. Reproducibility of metabolic measurements in malignant tumors using FDG PET. J Nucl Med 1999;40:1771–7.PubMedGoogle Scholar
  11. 11.
    Dehdashti F, Flanagan FL, Mortimer JE, Katzenellenbogen JA, Welch MJ, Siegel BA. Positron emission tomographic assessment of “metabolic flare” to predict response of metastatic breast cancer to antiestrogen therapy. Eur J Nucl Med 1999;26:51–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Spaepen K, Stroobants S, Dupont P, Bormans G, Balzarini J, Verhoef G, et al. [18F]FDG PET monitoring of tumour response to chemotherapy: does [18F]FDG uptake correlate with the viable tumour cell fraction? Eur J Nucl Med Mol Imaging 2003;30:682–8.PubMedCrossRefGoogle Scholar
  13. 13.
    van Waarde A, Cobben DC, Suurmeijer AJ, Maas B, Vaalburg W, de Vries EF, et al. Selectivity of 18F-FLT and 18F-FDG for differentiating tumor from inflammation in a rodent model. J Nucl Med 2004;45:695–700.PubMedGoogle Scholar
  14. 14.
    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]fluorothymidine-positron emission tomography imaging: evaluation of analytical methods. Cancer Res 2005;65:10104–12.PubMedCrossRefGoogle Scholar
  15. 15.
    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;8:36–42.PubMedCrossRefGoogle Scholar
  16. 16.
    Singletary SE, Allred C, Ashley P, Bassett LW, Berry D, Bland KI, et al. Revision of the American Joint Committee on Cancer staging system for breast cancer. J Clin Oncol 2002;20:3628–36.PubMedCrossRefGoogle Scholar
  17. 17.
    Cleij MC, Steel CJ, Brady F, Ell PJ, Pike VW, Luthra SK. An improved synthesis of 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) and the fate of the precursor 2,3′-anhydro-5′-O-(4,4′-dimethoxytrityl)-thymidine. J Labelled Compounds Radiopharm 2001;44 Suppl 1:871–3.Google Scholar
  18. 18.
    Shields AF, Grierson JR, Muzik O, Stayanoff JC, Lawhorn-Crews JM, Obradovich JE, et al. Kinetics of 3′-deoxy-3′-[F-18]fluorothymidine uptake and retention in dogs. Mol Imaging Biol 2002;4:83–9.PubMedCrossRefGoogle Scholar
  19. 19.
    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;196:167–73.PubMedGoogle Scholar
  20. 20.
    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;11:4341–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Archer CD, Parton M, Smith IE, Ellis PA, Salter J, Ashley S, et al. Early changes in apoptosis and proliferation following primary chemotherapy for breast cancer. Br J Cancer 2003;89:1035–41.PubMedCrossRefGoogle Scholar
  22. 22.
    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;44:1426–31.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Laura Kenny
    • 1
  • R. Charles Coombes
    • 1
    • 2
  • David M. Vigushin
    • 1
    • 2
  • Adil Al-Nahhas
    • 2
  • Sami Shousha
    • 2
  • Eric O. Aboagye
    • 1
    • 3
    Email author
  1. 1.Imperial College LondonLondonUK
  2. 2.Hammersmith Hospitals NHS TrustLondonUK
  3. 3.Molecular Therapy GroupHammersmith HospitalLondonUK

Personalised recommendations