[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 Kunming 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 1 h 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 cyclophosphamide, clear image on the tumor could be seen. 24 h after the treatment of cyclophosphamide, 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 1 h after cyclophosphamide treatment (4.00 +/- 0.38). At 24 h after cyclophosphamide treatment, TUNEL staining showed a significantly higher rate of apoptotic cells in the mice.


CONCLUSIONS
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 99mTc-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.
Lan
Xiao-li
XL
Department of Nuclear Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science & Technology, Hubei Key Laboratory of Molecular Imaging, Wuhan 430022, China.
Zhang
Yong-xue
YX
He
Yong
Y
Sun
Xun
X
An
Rui
R
Gao
Zai-rong
ZR
Cao
Guo-xiang
GX
D000818:Animals; D017304:Annexin A5 / Q000493:pharmacokinetics; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D003520:Cyclophosphamide / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011897:Random Allocation; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
D017304:Annexin A5; D018906:Antineoplastic Agents, Alkylating; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C117287:technetium Tc 99m HYNIC annexin V; D003520:Cyclophosphamide