Assessment of therapeutic himor response using ^99mTc- ethylenedicysteine-glucosamine

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 μCi/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.