In Vivo Imaging of Radiation Induced Apoptosis

Abstract

To evaluate the feasibility of 99mTc-HYNIC-annexinV for in vivo detection of apoptosis after single dose radiation, and to investigate the correlation between early apoptosis and radiosensitivity. The radiosensitive El4 lymphoma and radio-resistant S180 sarcoma cell lines were tested. Ten days after being inoculated with El4 lymphoma and S180 sarcoma separately in the right upper limbs, the mice were randomly divided into imaging group and observing group. The imaging group was injected with 99mTc-HYNIC-annexin V through tail vein and SPECT scanned after different doses of radiation. The observing groups did not receive 99mTc-HYNIC-annexin V and were observed for 2 weeks after being irradiated. All mice in the imaging group were sacrificed to evaluate the biodistribution of 99mTc in each tissue which were expressed as the percentage activity of injection dose per gram of tissue (%ID/g). The number of cell apoptosis was calculated with TUNEL. The intensity of apoptosis imaging on SPECT in E14 lymphoma significantly enhanced as the radiation dose escalated from 2 to 8 Gy. Tumor uptake of 99mTc-HYNIC-annexin V significantly correlated with the number of TUNEL-positive cells, which increased concordantly with the escalation of dose(r = 0.892, p = 0.000). With the same dose (0Gy or 8Gy), the value of %D/g,T/B,T/M and TUNEL-positive cells number of El4 lymphoma were significantly greater than those of S180 sarcoma. With 8 Gy, S180 sarcoma showed scarce apoptosis, no obvious tumor shrinkage was observed; the tumor growth was only retarded and re-growing on the 13th day after irradiation. El4 lymphoma entirely subsided after a single dose irradiation with 8Gy. 99mTc-HYNIC-annexin V can detect tumor apoptosis induced by radiation in vivo. After an 8 Gy single dose irradiation, the apoptosis of El4 lymphoma was significant, which correlated with the uptake of imaging agent and imaged clearly on 99mTc-HYNIC-annexin V SPECT. However, no significant apoptosis was observed either in vivo or in vitro study for S180 sarcoma with 8 Gy. The in vivo detected apoptosis after radiation by 99mTc-HYNIC-annexin V SPECT correlates well with radiation curability of tumor. Detection of apoptosis in tumor via 99mTc-HYNIC-annexin V can apply as a predictive index for radiotherapy.