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Abstract

Background

Positron emission tomography (PET) imaging using the radiotracers 18F-fluorodeoxyglucose (FDG) or 18F-fluorothymidine (FLT) has been proposed as imaging biomarkers of cell proliferation.

Purpose

To explore the correlations of FDG and FLT uptake with the Ki-67 labeling index in patients with lung cancer.

Material and Methods

Major databases were systematically searched for all relevant literature published in English. The correlation coefficient (rho) and its 95% confidence interval (CI) of individual studies were meta-analyzed using a random-effects model. The sources of heterogeneity were explored by subgroup analyses.

Results

Twenty-seven articles involving 1213 patients were included in this meta-analysis, comprising 22 studies for FDG uptake/Ki-67 expression correlation and eight for FLT uptake/Ki-67 expression correlation. The pooled rho values for 18F-FDG/Ki-67 correlation and 18F-FLT/Ki-67 correlation were 0.45 (95% CI, 0.41–0.50) and 0.65 (95% CI, 0.56–0.73), respectively, which indicated a moderate correlation for the former and a significant one for the latter. Although the subgroup analyses based on study design, scanner, sample method, and Ki-67 labeling method did not significantly explain the heterogeneity, these factors were potential sources of heterogeneity. In lung cancer, the pooled SUVmax of FDG uptake was significantly higher than that of FLT uptake (7.59 versus 3.86, P < 0.05). In addition, compared to FDG, FLT showed higher specificity yet lower sensitivity for the diagnosis of pulmonary lesions.

Conclusion

Both 18F-FDG and 18F-FLT correlate significantly with the Ki-67 labeling index in pulmonary lesions, and the latter, with a stronger correlation, may be more reliable for assessing tumor cell proliferation in lung cancer.

Keywords

Fluorothymidine fluorodeoxyglucose Ki-67 meta-analysis lung cancer

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References

Siegel

Zou

et al.

Cancer statistics, 2014. CA Cancer J Clin 2014; 64: 9–29.

Demura

Tsuchida

Ishizaki

et al.

18F-FDG accumulation with PET for differentiation between benign and malignant lesions in the thorax. J Nucl Med 2003; 44: 540–548.

Yamamoto

Nishiyama

Monden

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: 140–147.

Mac Manus

Hicks

Matthews

et al.

Positron emission tomography is superior to computed tomography scanning for response-assessment after radical radiotherapy or chemoradiotherapy in patients with non-small-cell lung cancer. J Clin Oncol 2003; 21: 1285–1292.

Ambrosini

Nicolini

Caroli

et al.

PET/CT imaging in different types of lung cancer: an overview. Eur J Radiol 2012; 81: 988–1001.

Higashi

Ueda

Arisaka

et al.

18F-FDG uptake as a biologic prognostic factor for recurrence in patients with surgically resected non-small cell lung cancer. J Nucl Med 2002; 43: 39–45.

Hicks

Kalff

MacManus

et al.

18F-FDG PET provides high-impact and powerful prognostic stratification in staging newly diagnosed non-small cell lung cancer. J Nucl Med 2001; 42: 1596–1604.

Shim

Lee

Kim

et al.

Non-small cell lung cancer: prospective comparison of integrated FDG PET/CT and CT alone for preoperative staging. Radiology 2005; 236: 1011–1019.

Buck

Schirrmeister

Guhlmann

et al.

Ki-67 immunostaining in pancreatic cancer and chronic active pancreatitis: does in vivo FDG uptake correlate with proliferative activity?

J Nucl Med 2001; 42: 721–725.

10.

Vesselle

Salskov

Turcotte

et al.

Relationship between non-small cell lung cancer FDG uptake at PET, tumor histology, and Ki-67 proliferation index. J Thorac Oncol 2008; 3: 971–978.

11.

Minamimoto

Toyohara

Seike

et al.

4'-[Methyl-11C]-thiothymidine PET/CT for proliferation imaging in non-small cell lung cancer. J Nucl Med 2012; 53: 199–206.

12.

Kaida

Kawahara

Hayakawa

et al.

The difference in relationship between 18F-FDG uptake and clinicopathological factors on thyroid, esophageal, and lung cancers. Nucl Med Commun 2014; 35: 36–43.

13.

Zhang

Cui

Tang

et al.

DW MRI at 3.0 T versus FDG PET/CT for detection of malignant pulmonary tumors. Int J Cancer 2014; 134: 606–611.

14.

Liu

Zhang

Cui

et al.

Preliminary comparison of diffusion-weighted MRI and PET/CT in predicting histological type and malignancy of lung cancer. Clin Respir J 2017; 11: 151–158.

15.

Shields

Grierson

Dohmen

et al.

Imaging proliferation in vivo with 18F-FLT and positron emission tomography. Nat Med 1998; 4: 1334–1336.

16.

Rasey

Grierson

Wiens

et al.

Validation of FLT uptake as a measure of thymidine kinase-1 activity in A549 carcinoma cells. J Nucl Med 2002; 43: 1210–1217.

17.

Buck

Schirrmeister

Hetzel

et al.

3-deoxy-3-[(18)F]fluorothymidine-positron emission tomography for noninvasive assessment of proliferation in pulmonary nodules. Cancer Res 2002; 62: 3331–3334.

18.

Vesselle

Grierson

Muzi

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: 3315–3323.

19.

Buck

Halter

Schirrmeister

et al.

Imaging proliferation in lung tumors with PET: 18F-FLT versus 18F-FDG. J Nucl Med 2003; 44: 1426–1431.

20.

Yang

Zhang

et al.

Imaging proliferation of 18F-FLT PET/CT correlated with the expression of microvessel density of tumour tissue in non-small-cell lung cancer. Eur J Nucl Med Mol Imaging 2012; 39: 1289–1296.

21.

Chen

Zhao

Gao

et al.

Proliferation PET image to characterize pathological spatial features in patients with non-small cell lung cancer: a pilot study. Int J Clin Exp Med 2015; 8: 9758–9764.

22.

Dittmann

Dohmen

Paulsen

et al.

18F-FLT PET for diagnosis and staging of thoracic tumours. Eur J Nucl Med Mol Imaging 2003; 30: 1407–1412.

23.

Nakasu

Fukami

et al.

Immunohistochemical proliferation markers may overestimate the growth potential after ionizing radiation: in vivo study in the rat anterior pituitary gland. Neurol Med Chir 2003; 43: 521–526. discussion 527.

24.

Rupinski

Dunlap

. Approximating Pearson product-moment correlations from Kendall’s tau and Spearman’s rho. Educ Psychol Meas 1996; 56: 419–429.

25.

Whiting

Rutjes

Westwood

et al.

QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 2011; 155: 529–536.

26.

Landis

Koch

. The measurement of observer agreement for categorical data. Biometrics 1977; 33: 159–174.

27.

Deng

Zhang

et al.

Correlation between the uptake of 18F-fluorodeoxyglucose (18F-FDG) and the expression of proliferation-associated antigen Ki-67 in cancer patients: a meta-analysis. PLoS One 2015; 10: e0129028–e0129028.

28.

Higgins

Thompson

. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539–1558.

29.

Chalkidou

Landau

Odell

et al.

Correlation between Ki-67 immunohistochemistry and 18F-fluorothymidine uptake in patients with cancer: A systematic review and meta-analysis. Eur J Cancer 2012; 48: 3499–3513.

30.

Yang

Ramnath

Moysich

et al.

Prognostic significance of MCM2, Ki-67 and gelsolin in non-small cell lung cancer. BMC Cancer 2006; 6: 203–203.

31.

Jakobsen

Sorensen

. Clinical impact of ki-67 labeling index in non-small cell lung cancer. Lung Cancer 2013; 79: 1–7.

32.

Warth

Cortis

Soltermann

et al.

Tumour cell proliferation (Ki-67) in non-small cell lung cancer: a critical reappraisal of its prognostic role. Br J Cancer 2014; 111: 1222–1229.

33.

Yamamoto

Nishiyama

Ishikawa

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 2007; 34: 1610–1616.

34.

Shim

Lee

Park

et al.

Relationship between FDG uptake and expressions of glucose transporter type 1, type 3, and hexokinase-II in Reed-Sternberg cells of Hodgkin lymphoma. Oncol Res 2009; 17: 331–337.

35.

Pauwels

Ribeiro

Stoot

et al.

FDG accumulation and tumor biology. Nucl Med Biol 1998; 25: 317–322.

36.

Everitt

Ball

Hicks

et al.

Differential (18)F-FDG and (18)F-FLT uptake on serial PET/CT imaging before and during definitive chemoradiation for non-small cell lung cancer. J Nucl Med 2014; 55: 1069–1074.

37.

Leimgruber

Moller

Everitt

et al.

Effect of platinum-based chemoradiotherapy on cellular proliferation in bone marrow and spleen, estimated by (18)F-FLT PET/CT in patients with locally advanced non-small cell lung cancer. J Nucl Med 2014; 55: 1075–1080.

38.

Scheffler

Zander

Nogova

et al.

Prognostic impact of [18F]fluorothymidine and [18F]fluoro-D-glucose baseline uptakes in patients with lung cancer treated first-line with erlotinib. PLoS One 2013; 8: e53081–e53081.

39.

Suleiman

Frechen

Scheffler

et al.

Modeling tumor dynamics and overall survival in advanced non-small-cell lung cancer treated with erlotinib. J Thorac Oncol 2015; 10: 84–92.

40.

Goodell

Krasinskas

Davison

et al.

Comparison of methods for proliferative index analysis for grading pancreatic well-differentiated neuroendocrine tumors. Am J Clin Pathol 2012; 137: 576–582.

41.

van Diest

van Dam

Henzen-Logmans

et al.

A scoring system for immunohistochemical staining: consensus report of the task force for basic research of the EORTC-GCCG. European Organization for Research and Treatment of Cancer-Gynaecological Cancer Cooperative Group. J Clin Pathol 1997; 50: 801–804.

42.

Fernebro

Engellau

Persson

et al.

Standardizing evaluation of sarcoma proliferation- higher Ki-67 expression in the tumor periphery than the center. APMIS 2007; 115: 707–712.

43.

Wang

Sui

et al.

Performance of FLT-PET for pulmonary lesion diagnosis compared with traditional FDG-PET: A meta-analysis. Eur J Radiol 2015; 84: 1371–1377.

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Correlations of 18F-FDG and 18F-FLT uptake on PET with Ki-67 expression in patients with lung cancer: a meta-analysis

Abstract

Background

Purpose

Material and Methods

Results

Conclusion

Keywords

Get full access to this article

References

Supplementary Material