Top

European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-02-2008 | Original Article

Comparison of ¹⁸F-FLT PET and ¹⁸F-FDG PET for preoperative staging in non-small cell lung cancer

Authors: Yuka Yamamoto, Yoshihiro Nishiyama, Naruhide Kimura, Shinya Ishikawa, Masaya Okuda, Shuji Bandoh, Nobuhiro Kanaji, Masato Asakura, Motoomi Ohkawa

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 2/2008

Abstract

Purpose

The nucleoside analog 3′-deoxy-3′-¹⁸F-fluorothymidine (FLT) has been introduced for imaging cell proliferation with positron emission tomography (PET). We prospectively compared the diagnostic efficacy of FLT PET with that of 2-deoxy-2-¹⁸F-fluoro-d-glucose (FDG) PET for the preoperative nodal and distant metastatic staging of non-small cell lung cancer (NSCLC).

Methods

A total of 34 patients with NSCLC underwent FLT PET and FDG PET. PET imaging was performed at 60 min after each radiotracer injection. The PET images were evaluated qualitatively for regions of focally increased metabolism. For visualized primary tumors, the maximum standardized uptake value (SUV) was calculated. Nodal stages were determined by using the American Joint Committee on Cancer staging system and surgical and histologic findings reference standards.

Results

For the depiction of primary tumor, sensitivity of FLT PET was 67%, compared with 94% for FDG PET (P = 0.005). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for lymph node staging on a per-patient basis were 57, 93, 67, 89, and 85%, respectively, with FLT PET and 57, 78, 36, 91, and 74%, respectively, with FDG PET (P > 0.1 for all comparisons). Two of the three distant metastases were detected with FLT and FDG PET.

Conclusion

In NSCLC, FLT PET showed better (although not statistically significant) specificity, positive predictive value and accuracy for N staging on a per-patient basis than FDG PET. However, FDG PET was found to have higher sensitivity for depiction of primary tumor than FLT PET.

Tanaka F, Yanagihara K, Otake Y, Miyahara R, Kawano Y, Nakagawa T, et al. Surgery for non-small cell lung cancer: postoperative survival based on the revised tumor-node-metastasis classification and its time trend. Eur J Cardiothorac Surg 2000;18:147–55.PubMedCrossRef

Barker JM, Silvestri GA. Lung cancer staging. Curr Opin Pulm Med 2002;8:287–93.PubMedCrossRef

McLoud TC, Bourgouin PM, Greenberg RW, Kosiuk JP, Templeton PA, Shepard JA, et al. Bronchogenic carcinoma: analysis of staging in the mediastinum with CT by correlative lymph node mapping and sampling. Radiology 1992;182:319–23.PubMed

Scott WJ, Gobar LS, Terry JD, Dewan NA, Sunderland JJ. Mediastinal lymph node staging of non-small-cell lung cancer: a prospective comparison of computed tomography and positron emission tomography. J Thorac Cardiovasc Surg 1996;111:642–8.PubMedCrossRef

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

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 2002;44:540–8.

Gould MK, Kuschner WG, Rydzak CE, Maclean CC, Demas AN, Shigemitsu H, et al. Test performance of positron emission tomography and computed tomography for mediastinal staging in patients with non-small-cell lung cancer: a meta-analysis. Ann Intern Med 2003;139:879–92.PubMed

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 chemoradiotherapy in non-small cell lung cancer. Eur J Nucl Med Mol Imaging 2006;33:140–7.PubMedCrossRef

Shreve PD, Anzai Y, Wahl RL. Pitfalls in oncologic diagnosis with FDG PET imaging: physiologic and benign variants. Radiographics 1999;19:61–77.PubMed

10.

Langen KJ, Braun U, Rota Kops E, Herzog H, Kuwert T, Nebeling B, et al. The influence of plasma glucose levels on fluorine-18-fluorodeoxyglucose uptake in bronchial carcinomas. J Nucl Med 1993;34:355–9.PubMed

11.

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

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;4:1334–6.PubMedCrossRef

13.

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

14.

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.PubMed

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

16.

Buck AK, Hetzel M, Schirrmeister H, Halter G, 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.PubMedCrossRef

17.

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.PubMedCrossRef

18.

Cobben DC, Elsinga PH, Hoekstra HJ, Suurmeijer AJ, 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

19.

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

20.

AJCC cancer staging manual. 6th ed. New York, NY: Springer, 2002; pp 165–77.

21.

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

22.

Mountain CF, Dresler CM. Regional lymph node classification for lung cancer staging. Chest 1997;111:1718–23.PubMed

23.

Yoon YC, Lee KS, Shim YM, Kim BT, Kim K, Kim TS. Metastasis to regional lymph nodes in patients with esophageal squamous cell carcinoma: CT versus FDG PET for presurgical detection-prospective study. Radiology 2003;227:764–70.PubMedCrossRef

24.

Kubota R, Yamada S, Kubota K, Ishiwata K, Tamahashi N, Ido T. Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. J Nucl Med 1992;33:1972–80.PubMed

25.

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

26.

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.PubMedCrossRef

27.

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.PubMed

28.

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

29.

Cobben DC, van der Laan BF, Maas B, Vaalburg W, Suurmeijer AJ, 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

30.

Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions. JAMA 2001;285:914–24.PubMedCrossRef

31.

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.PubMedCrossRef

32.

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

33.

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.PubMedCrossRef

34.

Costa A, Silvestrini R, Mochen C, Leguaglie 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

35.

Puglisi F, Minisini AM, Aprile G, Barbone F, Cataldi P, Artico D, et al. Balance between cell division and cell death as predictor of survival in patients with non-small-cell lung cancer. Oncology 2002;63:76–83.PubMedCrossRef

36.

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;61:2500–4.PubMed

37.

Pence JC, Kerns BJ, Dodge RK, Iglehart JD. Prognostic significance of the proliferation index in surgically resected non-small-cell lung cancer. Arch Surg 1993;128:1382–90.PubMed

Title: Comparison of 18F-FLT PET and 18F-FDG PET for preoperative staging in non-small cell lung cancer
Authors: Yuka Yamamoto
Yoshihiro Nishiyama
Naruhide Kimura
Shinya Ishikawa
Masaya Okuda
Shuji Bandoh
Nobuhiro Kanaji
Masato Asakura
Motoomi Ohkawa
Publication date: 01-02-2008
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 2/2008
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-007-0613-0

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Comparison of ¹⁸F-FLT PET and ¹⁸F-FDG PET for preoperative staging in non-small cell lung cancer

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 2/2008

Evaluation of [18F]-choline PET/CT for staging and restaging of prostate cancer

Radioguided occult lesion localisation in breast cancer using an intraoperative portable gamma camera: first results

Contralateral or bilateral lymph drainage revealed by breast lymphoscintigraphy

Impact of dual-time-point 18F-FDG PET imaging and partial volume correction in the assessment of solitary pulmonary nodules

Prognostic study of risk stratification among Japanese patients with ischemic heart disease using gated myocardial perfusion SPECT: J-ACCESS study

Wavelet denoising for voxel-based compartmental analysis of peripheral benzodiazepine receptors with 18F-FEDAA1106