Early Detection of Tumor Response by FLT/MicroPET Imaging in a C26 Murine Colon Carcinoma Solid Tumor Animal Model

Jenn-Tzong Chen,Wan-Chi Lee,Yu-Hsien Wu,Chih-Hsien Chang,Chung-Li Ho,Ying-Ling Wang,Te-Wei Lee,Liang-Cheng Chen

doi:10.1155/2011/535902

Jenn-Tzong Chen, Wan-Chi Lee + Show 6 more

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https://doi.org/10.1155/2011/535902

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Abstract

Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging demonstrated the change of glucose consumption of tumor cells, but problems with specificity and difficulties in early detection of tumor response to chemotherapy have led to the development of new PET tracers. Fluorine-18-fluorothymidine (18F-FLT) images cellular proliferation by entering the salvage pathway of DNA synthesis. In this study, we evaluate the early response of colon carcinoma to the chemotherapeutic drug, lipo-Dox, in C26 murine colorectal carcinoma-bearing mice by 18F-FDG and 18F-FLT. The male BALB/c mice were bilaterally inoculated with 1 × 105 and 1 × 106 C26 tumor cells per flank. Mice were intravenously treated with 10 mg/kg lipo-Dox at day 8 after 18F-FDG and 18F-FLT imaging. The biodistribution of 18F-FDG and 18F-FLT were followed by the microPET imaging at day 9. For the quantitative measurement of microPET imaging at day 9, 18F-FLT was superior to 18F-FDG for early detection of tumor response to Lipo-DOX at various tumor sizes (P < 0.05). The data of biodistribution showed similar results with those from the quantification of SUV (standard uptake value) by microPET imaging. The study indicates that 18F-FLT/microPET is a useful imaging modality for early detection of chemotherapy in the colorectal mouse model.

Highlights

18F-fluorodeoxyglucose (18F-FDG) is widely used as a noninvasive marker in clinical oncology. 18F-FDG, an analog of glucose, undergoes phosphorylation by hexokinase, cannot further enter glycolysis, and is trapped in the cell. 18FFDG has high-detection sensitivity, but not specificity; the property showed the difficulty of distinguishing proliferation tumor cells from inflammatory cells, making it less suitable as a marker for studying drug response [1,2,3]
Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging demonstrated the change of glucose consumption of tumor cells, but problems with specificity and difficulties in early detection of tumor response to chemotherapy have led to the development of new PET tracers
For the quantitative measurement of microPET imaging at day 9, 18F-FLT was superior to 18F-FDG for early detection of tumor response to Lipo-DOX at various tumor sizes (P < 0.05)

Summary

Introduction

18F-fluorodeoxyglucose (18F-FDG) is widely used as a noninvasive marker in clinical oncology. 18F-FDG, an analog of glucose, undergoes phosphorylation by hexokinase, cannot further enter glycolysis, and is trapped in the cell. 18FFDG has high-detection sensitivity, but not specificity; the property showed the difficulty of distinguishing proliferation tumor cells from inflammatory cells, making it less suitable as a marker for studying drug response [1,2,3]. Because 18FFDG is metabolized in nontumor tissues, the results may be false-positive in inflammation or reactive tissue [4, 5]. For these reasons, 18F-FDG is not suitable as a marker for early response to treatment of cancer. 18F-FDG is not suitable as a marker for early response to treatment of cancer Another approach for tumor visualization is using radiolabeled nucleosides such as 11C-thymidine. The halflife of 11C-thymidine and the poor imaging quality limit its clinical application. These limitations led to the development of analogues that are more resistant to degradation and can be labeled with radionuclides more conductive to routine clinical use, such as 18F [6]

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