In vivo99mTc-HYNIC-annexin V imaging of early tumor apoptosis in mice after single dose irradiation.
BACKGROUND
Apoptosis is a major mode of hematological tumor death after radiation. Early detection of apoptosis may be beneficial for cancer adaptive treatment. 99mTc-HYNIC-annexinV has been reported as a promising agent for in vivo apoptosis imaging. The purpose of this study is to evaluate the feasibility of in vivo99mTc-HYNIC-annexinV imaging of radiation- induced apoptosis, and to investigate its correlation with radiosensitivity.


METHODS
Ten days after inoculation of tumor cells in the right upper limbs, the mice were randomly divided into two groups. The imaging group (4 mice each level, 4 dose levels) was injected with 4-8 MBq 99mTc-HYNIC-annexinV 24 hours after irradiation and imaged 1 hr post-injection, and the mice were sacrificed immediately after imaging for biodistribution analysis of annexin V. The observation group (4 mice each level, 2 dose levels) was only observed for tumor regression post-radiation. The number of apoptotic cells in a tumor was estimated with TUNEL assay.


RESULTS
The 99mTc-HYNIC-annexin V uptake in E14 lymphoma significantly increased as the radiation dose escalated from 0 to 8 Gy, and significantly correlated with the number of TUNEL-positive cells (r = 0.892, P < 0.001). The Annexin-V uptake and the number of TUNEL-positive cells in El4 lymphoma were significantly greater than those in S180 sarcoma. With 8 Gy, S180 sarcoma tumor showed scanty apoptosis and less shrinkage while El4 lymphoma showed remarkable apoptosis and complete remission.


CONCLUSIONS
99mTc-HYNIC-annexinV in vivo imaging is a feasible method to detect early radiation-induced apoptosis in different tumors, and might be predictive for radiation sensitivity.
Guo
Ming-fang
MF
Division of Abdominal Tumor, Cancer center, West China Hospital, Sichuan University, Sichuan, PR China. GMF@yahoo.com.cn
Zhao
Yaqing
Y
Tian
Rong
R
Li
Lin
L
Guo
Leiming
L
Xu
Feng
F
Liu
Yong-mei
YM
He
Yong-bo
YB
Bai
Sen
S
Wang
Jin
J
D000818:Animals; D017304:Annexin A5; D017209:Apoptosis / Q000528:radiation effects*; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000532:radiotherapy; D015609:Organotechnetium Compounds; D011836:Radiation Tolerance; D011877:Radionuclide Imaging / Q000379:methods; D019275:Radiopharmaceuticals
D017304:Annexin A5; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C117287:technetium Tc 99m HYNIC annexin V