[Feasibility of apoptosis-imaging agent 99mTc-HYNIC-annexin V in early assessment of chemotherapeutic effect on tumor models].

Objective To evaluate if ^99mTc-HYNIC-annexin Ⅴ may be used to detect the early chemotherapeutic effect and to determine the best timing for detecting apoptosis in vivo. Methods Annexin Ⅴ was labeled with ^99mTc using HYNIC as a bifunctional agent. Normal Kumning mice received inoculation of Ehrlich ascites cells into the right upper limb. After the tumor reached 1 cm in diameter, the mice were randomly divided into saline treatment group as control and cyclophosphamide （150 mg/kg injected intraperitoneally） treatment group. ^99mTc-HYNIC-annexin Ⅴ was injected intravenously at 1h and 24 h after treatment. Region of interest technique （ROI） from the SPECT images taken at different time was used to get the ratio of tumor/limb in each group. TUNEL staining was used to detect apoptotic cells and the rates of positive stained cells were calculated. Results After treatment with saline, only little amount of the radiolabeled tracer could be seen in the tumor and showed weak image of the tumor. But after 24 h of treatment with cyelophosphamide, clear image on the tumor could be seen. 24 h after the treatment of eyclophosphamide, the ratio of tumor/limb was （6.27 ± 0.24） which was much higher than that at 24 h after treatment with saline （2.36 ± 0.18 ） and that at 1h after cyclophosphamide treatment （4. 00 ± 0.38 ）. At 24 h after cyciophosphamide treatment, TUNEL staining showed a significantly higher rate of apoptotic cells in the mice. Conclusion ^99mTc-HYNIC-annexin Ⅴ can be used as an apoptosis-imaging agent to detect and evaluate the early curative effect after chemotherapy. The effective detection of apoptotic response in tumor with ^99Tc-HYNIC-annexin Ⅴ requires a 24 h interval after chemotherapy. SPECT images can be obtained at 60 min after injection of the imaging agent. It suggests that ^99mTc-HYNIC-annexin Ⅴ may become a promising agent for apoptosis-imaging in clinical application. Key words: Annexin Ⅴ ;  Apoptosis ;  Radionuclide imaging;  Chemotherapy