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Correlation of 18F-FLT and 18F-FDG uptake on PET with Ki-67 immunohistochemistry in non-small cell lung cancer

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The nucleoside analogue 3′-deoxy-3′-18F-fluorothymidine (FLT) has recently been introduced for imaging cell proliferation with positron emission tomography (PET). We prospectively evaluated whether FLT uptake reflects proliferative activity as indicated by the Ki-67 index in non-small cell lung cancer (NSCLC), in comparison with 2-deoxy-2-18F-fluoro-D-glucose (FDG).

Methods

A total of 18 patients with newly diagnosed NSCLC were examined with both FLT PET and FDG PET. PET imaging was performed at 60 min after each radiotracer injection. Tumour lesions were identified as areas of focally increased uptake, exceeding background uptake in the lungs. For semi-quantitative analysis, the maximum standardised uptake value (SUV) was calculated. Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens. Immunohistochemical findings were correlated with SUVs.

Results

The sensitivity of FLT and FDG PET for the detection of lung cancer was 72% and 89%, respectively. Four of the five false-negative FLT PET findings occurred in bronchiolo-alveolar carcinoma. The mean FLT SUV was significantly lower than the mean FDG SUV. A significant correlation was observed between FLT SUV and Ki-67 index (r = 0.77; p < 0.0002) and for FDG SUV (r = 0.81; p < 0.0001).

Conclusion

The results of this preliminary study suggest that, compared with FDG, FLT may be less sensitive for primary staging in patients with NSCLC. Although FLT uptake correlated significantly with proliferative activity in NSCLC, the correlation was not better than that for FDG uptake.

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References

  1. Rohren EM, Turkington TG, Coleman RE. Clinical applications of PET in oncology. Radiology 2004;231:305–32.

    Article  PubMed  Google Scholar 

  2. Demura Y, Tsuchida T, Ishizaki T, Mizuno S, Totani Y, Ameshima S, et al. 18F-FDG accumulation with PET for differentiation between benign and malignant lesions in the thorax. J Nucl Med 2003;44:540–8.

    PubMed  CAS  Google Scholar 

  3. Ryu JS, Choi NC, Fischman AJ, Lynch TJ, Mathisen DJ. FDG-PET in staging and restaging non-small cell lung cancer after neoadjuvant chemoradiotherapy: correlation with histopathology. Lung Cancer 2002;35:179–87.

    Article  PubMed  Google Scholar 

  4. Yamamoto Y, Nishiyama Y, Monden T, Sasakawa Y, Ohkawa M, Gotoh M, et al. Correlation of FDG-PET findings with histopathology in the assessment of response to induction vhemoradiotherapy in non-small cell lung cancer. Eur J Nucl Med Mol Imaging 2006;33:140–7.

    Article  PubMed  Google Scholar 

  5. Costa A, Silvestrini R, Mochen C, Lequaglie C, Boracchi P, Faranda A, et al. P53 expression, DNA ploidy and S-phase cell fraction in operable locally advanced non-small-cell lung cancer. Br J Cancer 1996;73:914–9.

    PubMed  CAS  Google Scholar 

  6. Shields AF, Larson SM, Grunbaum Z, Graham MM. Short-term thymidine uptake in normal and neoplastic tissues: studies for PET. J Nucl Med 1984;25:759–64.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  8. Rasey JS, Grierson JR, Wiens LW, Kolb PD, Schwartz JC. Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells. J Nucl Med 2002;43:1210–7.

    PubMed  CAS  Google Scholar 

  9. 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;52:1602–6.

    Article  PubMed  CAS  Google Scholar 

  10. van Westreenen H, Cobben DCP, 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;46:400–4.

    PubMed  Google Scholar 

  11. Smyczek-Gargya B, Fersis N, Dittmann H, Vogel U, Reischl G, Machulla H-J, et al. PET with [18F]fluorothymidine for imaging of primary breast cancer: a pilot study. Eur J Nucl Med Mol Imaging 2004;31:720–4.

    Article  PubMed  Google Scholar 

  12. Cobben DC, Van der Laan BF, Maas B, Vaalburg W, Suumeijer AJH, Hoekstra HJ, et al. 18F-FLT PET for visualization of laryngeal cancer: comparison with 18F-FDG PET. J Nucl Med 2004;45:226–31.

    PubMed  Google Scholar 

  13. Buck AK, Hetzel M, Schirrmeister H, Halter J, Moller P, Kratochwil C, et al. Clinical relevance of imaging proliferative activity in lung nodules. Eur J Nucl Med Mol Imaging 2005;32:525–33.

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  15. 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;8:3315–32.

    PubMed  CAS  Google Scholar 

  16. 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;62:3331–4.

    PubMed  CAS  Google Scholar 

  17. Yap CS, Czernin J, Fishbein MC, Cameron RB, Schiepers C, Phelps ME, et al. Evaluation of thoracic tumors with18F-fluorothymidine and18F-fluorodeoxyglucose-positron emission tomography. Chest 2006;129:393–401.

    Article  PubMed  Google Scholar 

  18. 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;30:1407–12.

    Article  PubMed  CAS  Google Scholar 

  19. Machulla HJ, Blocher A, Kuntzsch M, Piert M, Wei R, Grierson JR. Simplified labeling approach for synthesizing 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT). J Radioanal Nucl Chem 2000;24:843–6.

    Article  Google Scholar 

  20. Dosaka-Akita H, Hommura F, Mishina T, Ogura S, Shimizu M, Katoh H, et al. A risk-stratification model of non-small cell lung cancers using cyclin E, ki-67, and ras p21: different roles of G1 cyclins in cell proliferation and prognosis. Cancer Res 2001;6:2500–4.

    Google Scholar 

  21. D’Amico TA, Aloia TA, Moore MB, Herndon II JE, Brooks KR, Lau CL, et al. Molecular biologic substaging of stage I lung cancer according to gender and histology. Ann Thorac Surg 2000;69:882–6.

    Article  PubMed  CAS  Google Scholar 

  22. Vesselle H, Schmidt RA, Pugsley JM, Li M, Kohlmeyer SG, Valliéres E, et al. Lung cancer proliferation correlates with [F-18]fluorodeoxyglucose uptake by positron emission tomography. Clin Cancer Res 2000;6:3837–44.

    PubMed  CAS  Google Scholar 

  23. 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;41:85–92.

    PubMed  CAS  Google Scholar 

  24. Vansteenkiste JF, Stroobants SG, Dupont PJ, De Leyn PR, Verbeken EK, Deneffe GJ, et al. Prognostic importance of the standardized uptake value on18F-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 1999;17:3201–6.

    PubMed  CAS  Google Scholar 

  25. Mac Manus MP, Hicks RJ, Ball DL, Kalff V, Ware R, Wirth A, et al. F-18 fluorodeoxyglucose positron emission tomography staging in radical radiotherapy candidates with nonsmall cell lung carcinoma: powerful correlation with survival and high impact on treatment. Cancer 2001;92:886–95.

    Article  PubMed  CAS  Google Scholar 

  26. Mier W, Haberkorn U, Eisenhut M. [18F]FLT; portrait of a proliferation marker. Eur J Nucl Med Mol Imaging 2002;29:165–9.

    Article  PubMed  CAS  Google Scholar 

  27. Grierson JR, Shields AF. Radiosynthesis of 3′-deoxy-3′-[18F]fluorothymidine: [18F]FLT for imaging of cellular proliferation in vivo. Nucl Med Biol 2000;27:143–56.

    Article  PubMed  CAS  Google Scholar 

  28. Cobben DC, Elsinga PH, Hoekstra HJ, Suurmeijer AJH, Vaalburg W, Maas B, et al. Is 18F-3′-fluoro-3′-deoxy-L-thymidine useful for the staging and restaging of non-small cell lung cancer? J Nucl Med 2004;45:1677–82.

    PubMed  CAS  Google Scholar 

  29. Wienhard K, Eriksson L, Grootoonk S, Casey M, Pietrzyk U, Heiss WD. Performance evaluation of the positron scanner ECAT EXACT. J Comput Assist Tomogr 1992;16:804–13.

    Article  PubMed  CAS  Google Scholar 

  30. Lartizien C, Comtat C, Kinahan PE, Ferreira N, Bendriem B, Trebossen R. Optimization of injected dose based on noise equivalent count rates for 2- and 3-dimensional whole body PET. J Nucl Med 2002;43:1268–78.

    PubMed  Google Scholar 

  31. Raylman R, Kison P, Wahl RL. Capabilities of two- and three-dimensional FDG-PET for detecting small lesions and lymph nodes in the upper torso: a dynamic phantom study. Eur J Nucl Med 1999;26:39–45.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Radiology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan

    Yuka Yamamoto, Yoshihiro Nishiyama & Motoomi Ohkawa

  2. Second Department of Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Shinya Ishikawa, Jun Nakano & Sung Soo Chang

  3. First Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Shuji Bandoh & Nobuhiro Kanaji

  4. Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Reiji Haba & Yoshio Kushida

Authors
  1. Yuka Yamamoto
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  2. Yoshihiro Nishiyama
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  3. Shinya Ishikawa
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  4. Jun Nakano
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  5. Sung Soo Chang
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  10. Motoomi Ohkawa
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Correspondence to Yuka Yamamoto.

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Yamamoto, Y., Nishiyama, Y., Ishikawa, S. et al. Correlation of 18F-FLT and 18F-FDG uptake on PET with Ki-67 immunohistochemistry in non-small cell lung cancer. Eur J Nucl Med Mol Imaging 34, 1610–1616 (2007). https://doi.org/10.1007/s00259-007-0449-7

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  • DOI: https://doi.org/10.1007/s00259-007-0449-7

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