Abstract
Purpose
To compare the diagnostic efficacies of 18F-FLT and 18F-FDG PET/CT in non-small-cell lung cancer (NSCLC), focusing on the correlation between FLT and FDG tumour uptake and tumour cell proliferation as indicated by the cyclin D1 labelling index.
Methods
A total of 31 patients with NSCLC underwent FLT and FDG PET/CT scanning followed by surgery. PET/CT images were compared with the pathology. Tumour cell proliferation was assessed by cyclin D1 immunohistochemistry.
Results
The sensitivities of FLT and FDG PET/CT for the primary lesion were 74% and 94%, respectively (p=0.031). For N staging, 77% patients were correctly staged, 6% overstaged, 16% understaged by FLT, while the values for FDG were 77%, 16% and 6%, respectively. The sensitivity, specificity, accuracy, and positive predictive value with FLT for lymph nodes were 65%, 98%, 93% and 89%, respectively, and 85%, 84%, 84% and 52% with FDG (p<0.01).Tumour SUV of FLT was significantly correlated with the cyclin D1 labelling index (r=0.644; p<0.01), but the SUV of FDG was not significantly correlated (r=0.293; p>0.05).
Conclusion
In terms of N staging, FLT PET/CT resulted in understaging of more patients but overstaging of fewer patients, and for regional lymph nodes showed better specificity, accuracy and positive predictive value than FDG PET/CT in NSCLC. Tumour FLT uptake was correlated with tumour cell proliferation as indicated by the cyclin D1 labelling index, suggesting that further studies are needed to evaluate the use of FLT PET/CT for the assessment of therapy response to anticancer drugs.
Similar content being viewed by others
References
Yamamoto Y, Nishiyama Y, Monden T, et al. Correlation of FDG-PET findings with histopathology in the assessment of response to induction chemoradiotherapy in non-small cell lung cancer. Eur J Nucl Med Mol Imaging 2006;33:140–7.
Shim SS, Lee KS, Kim BT, et al. Non-small cell lung cancer: prospective comparison of integrated FDG PET/CT and CT alone for preoperative staging. Radiology 2005;236:1011–9.
Yang W, Fu Z, Yu J, et al. Value of PET/CT versus enhanced CT for locoregional lymph nodes in non-small cell lung cancer. Lung Cancer 2008;61:35–43.
Mier W, Haberkorn U, Eisenhut M. [18F]FLT: portrait of a proliferation marker. Eur J Nucl Med 2002;29:165–9.
Martin B, Paesmans M, Mascaux C, et al. Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis. Br J Cancer 2004;91:2018–25.
Au NH, Cheang M, Huntsman DG, et al. Evaluation of immunohistochemical markers in non-small cell lung cancer by unsupervised hierarchical clustering analysis: a tissue microarray study of 284 cases and 18 markers. J Pathol 2004;204:101–9.
Saitoh G, Sugio K, Ishida T, et al. Prognostic significance of p21waf1, cyclin D1 and retinoblastoma expression detected by immunohistochemistry in non-small cell lung cancer. Oncol Rep 2001;8:737–43.
Jin M, Inoue S, Umemura T, et al. Cyclin D1, p16 and retinoblastoma gene product expression as a predictor for prognosis in non-small cell lung cancer at stages I and II. Lung Cancer 2001;34:207–18.
Oshita F, Ito H, Ikehara M, et al. Prognostic impact of survivin, cyclin D1, integrin beta1, and VEGF in patients with small adenocarcinoma of stage I lung cancer. Am J Clin Oncol 2004;27:425–8.
Buck AK, Schirrmeister H, Hetzel M, et al. 3-deoxy-3-[(18)F]fluorothymidine-positron emission tomography for noninvasive assessment of proliferation in pulmonary nodules. Cancer Res 2002;62:3331–4.
Vesselle H, Grierson J, Muzi M, 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;8:3315–23.
Goldstraw P, Crowley J, Chansky K, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2007;2:706–14.
Yamamoto Y, Nishiyama Y, Kimura N, et al. Comparison of (18)F-FLT PET and (18)F-FDG PET for preoperative staging in non-small cell lung cancer. Eur J Nucl Med Mol Imaging 2008;35:236–45.
Tian J, Yang X, Yu L, Chen P, Xin J, Ma L, et al. A multicenter clinical trial on the diagnostic value of dual-tracer PET/CT in pulmonary lesions using 3′-deoxy-3′-18F-fluorothymidine and 18F-FDG. J Nucl Med 2008;49:186–94.
Marom EM, Aloia TA, Moore MB, et al. Correlation of FDG-PET imaging with Glut-1 and Glut-3 expression in early-stage non-small cell lung cancer. Lung Cancer 2001;33:99–107.
Rasey JS, Grierson JR, Wiens LW, et al. Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells. J Nucl Med 2002;43:1210–7.
Schwartz JL, Tamura Y, Jordan R, et al. Monitoring tumor cell proliferation by targeting DNA synthetic processes with thymidine and thymidine analogs. J Nucl Med 2003;44:2027–32.
Dimitrakopoulou-Strauss A, Strauss LG. The role of 18F-FLT in cancer imaging: does it really reflect proliferation? Eur J Nucl Med Mol Imaging 2008;35:523–6.
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;65:4202–10.
Reske SN, Deisenhofer S. Is 3′-deoxy-3′-(18)F-fluorothymidine a better marker for tumour response than (18)F-fluorodeoxyglucose? Eur J Nucl Med Mol Imaging 2006;33 Suppl 1:38–43.
Wieder HA, Geinitz H, Rosenberg R, et al. PET imaging with [18F]3′-deoxy-3′-fluorothymidine for prediction of response to neoadjuvant treatment in patients with rectal cancer. Eur J Nucl Med Mol Imaging 2007;34:878–83.
Yap CS, Czernin J, Fishbein MC, et al. Evaluation of thoracic tumors with 18F-fluorothymidine and 18F-fluorodeoxyglucose-positron emission tomography. Chest 2006;129:393–401.
Troost EG, Vogel WV, Merkx MA, et al. 18F-FLT PET does not discriminate between reactive and metastatic lymph nodes in primary head and neck cancer patients. J Nucl Med 2007;48:726–35.
Kato JY, Matsuoka M, Strom DK, et al. Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase. Mol Cell Biol 1994;4:2713–21.
Gautschi O, Ratschiller D, Gugger M, et al. Cyclin D1 in non-small cell lung cancer: a key driver of malignant transformation. Lung Cancer 2007;55:1–14.
Ratschiller D, Heighway J, Gugger M, et al. Cyclin D1 overexpression in bronchial epithelia of patients with lung cancer is associated with smoking and predicts survival. J Clin Oncol 2003;21:2085–93.
Benzeno S, Lu F, Guo M, et al. Identification of mutations that disrupt phosphorylation-dependent nuclear export of cyclin D1. Oncogene 2006;25:6291–303.
Soomro IN, Holmes J, Whimster WF. Predicting prognosis in lung cancer: use of proliferation marker, Ki67 monoclonal antibody. J Pak Med Assoc 1998;48:66–9.
Zhou P, Jiang W, Zhang YJ, et al. Antisense to cyclin D1 inhibits growth and reverses the transformed phenotype of human esophageal cancer cells. Oncogene 1995;11:571–80.
Fry DW, Harvey PJ, Keller PR, et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD-0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther 2004;3:1427–38.
Leyton J, Smith G, Lees M, et al. Noninvasive imaging of cell proliferation following mitogenic extracellular kinase inhibition by PD0325901. Mol Cancer Ther 2008;7:3112–21.
Arnér ES, Eriksson S. Mammalian deoxyribonucleoside kinases. Pharmacol Ther 1995;67:155–86.
Hoffman EJ, Huang SC, Phelps ME. Quantitation in positron emission computed tomography: 1. Effect of object size. J Comput Assist Tomogr 1979;3:299–308.
Soret M, Bacharach SL, Buvat I. Partial-volume effect in PET tumor imaging. J Nucl Med 2007;48:932–45.
Rousset O, Rahmim A, Alavi A, et al. Partial volume correction strategies in PET. PET Clinics 2007;2:235–49.
Pottgen C, Levegrun S, Theegarten D, et al. Value of 18F-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography in non-small-cell lung cancer for prediction of pathologic response and times to relapse after neoadjuvant chemoradiotherapy. Clin Cancer Res 2006;12:97–106.
Hickeson M, Yun M, Matthies A, et al. Use of a corrected standardized uptake value based on the lesion size on CT permits accurate characterization of lung nodules on FDG-PET. Eur J Nucl Med Mol Imaging 2002;29:1639–47.
Vesselle H, Schmidt RA, Pugsley JM, et al. Lung cancer proliferation correlates with F-18 fluorodeoxyglucose uptake by positron emission tomography. Clin Cancer Res 2000;6:3837–44.
Jaskowiak CJ, Bianco JA, Perlman SB, Fine JP. Influence of reconstruction iterations on 18F-FDG PET/CT standardized uptake values. J Nucl Med 2005;46:424–8.
Acknowledgments
This work was supported by the Research Fund of Shandong Provincial Health Bureau of China (grant 2009HZ088), and by the Research Fund of Shandong Cancer Hospital and Institute (no. 2009-11).
Conflicts of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yang, W., Zhang, Y., Fu, Z. et al. Imaging of proliferation with 18F-FLT PET/CT versus 18F-FDG PET/CT in non-small-cell lung cancer. Eur J Nucl Med Mol Imaging 37, 1291–1299 (2010). https://doi.org/10.1007/s00259-010-1412-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-010-1412-6