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.
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References
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.
Barker JM, Silvestri GA. Lung cancer staging. Curr Opin Pulm Med 2002;8:287–93.
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.
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.
Rohren EM, Turkington TG, Coleman RE. Clinical applications of PET in oncology. Radiology 2004;231:305–32.
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.
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.
Shreve PD, Anzai Y, Wahl RL. Pitfalls in oncologic diagnosis with FDG PET imaging: physiologic and benign variants. Radiographics 1999;19:61–77.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
AJCC cancer staging manual. 6th ed. New York, NY: Springer, 2002; pp 165–77.
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.
Mountain CF, Dresler CM. Regional lymph node classification for lung cancer staging. Chest 1997;111:1718–23.
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.
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.
Mier W, Haberkorn U, Eisenhut M. [18F]FLT; portrait of a proliferation marker. Eur J Nucl Med Mol Imaging 2002;29:165–9.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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Yamamoto, Y., Nishiyama, Y., Kimura, N. et al. Comparison of 18F-FLT PET and 18F-FDG PET for preoperative staging in non-small cell lung cancer. Eur J Nucl Med Mol Imaging 35, 236–245 (2008). https://doi.org/10.1007/s00259-007-0613-0
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DOI: https://doi.org/10.1007/s00259-007-0613-0