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Assessment of therapeutic tumor response using 99mtc-ethylenedicysteine-glucosamine
David Yang1, Masashi Yukihiro, Dong-Fang Yu
1Divisioni of Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. dyang@di.mdacc.tmc.edu
Purpose:
The aim of this study was to evaluate 99mTc-ethylenedicysteine-glucosamine (EC-DG) for the assessment of tumor growth.
Method:
To evaluate whether 99mTc-EC-DG is involved in cell nuclei activity, in vitro thymidine incorporation, and cell-cycle assays of EC-DG were conducted using lung and breast cancer cells. Biodistribution of 99mTc-EC-DG in lung tumor-bearing mice (0.5-4 hours, 1 Ci/mouse, i. v.) was used to estimate the radiation-absorbed dose. Autoradiograms of 99mTc-EC-DG and 18F-FDG were compared in nude mice bearing uterine sarcoma. Rabbits inoculated with VX-2 cells were imaged with 99mTc-EC-DG and 99mTc-EC. For therapeutic assessment studies, scintigraphic imaging studies with 99mTc-EC-DG in mammary tumor-bearing rats were conducted at various days after treatment with paclitaxel and cisplatin. The imaging findings were correlated immunohistochemical assays (mRNA expression, apoptosis, and cell-cycle changes in tumor), and flow cytometry analysis was performed.
Results:
In vitro cellular uptake assays indicated that cell nuclei activity could be assessed by 99mTc-EC-DG. Scintigraphy and autoradiograms in animal models demonstrated that the tumor could be clearly visualized by 99mTc-EC-DG. The efficacy of paclitaxel and cisplatin treatment in rodent models could be assessed using tumor/muscle ratios. Immunohistochemical staining indicated a reduced expression of bFGF and an increased apoptosis and cell-cycle changes after paclitaxel and cisplatin treatment.
Conclusion:
99mTc-EC-DG is involved in cell nuclei activity and could assess the therapeutic tumor response.
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