Study on mice tumor-bearing cell apoptosis imaging in vivo after a single dose of chemotherapy

Abstract

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Objectives: To investigate the effectiveness and feasibility of cell apoptosis imaging in vivo of tumor response after a single dose of chemotherapy

Methods: 99Tcm-HYNIC-AnnexinV as cell apoptosis molecular probe was obtained through chemical and radiochemical synthesis. Seven days after being inoculated with S-180 sarcoma in the right upper limbs, the mice weighed 20~25 g were randomized to receive a single dose of Cyclophosphamide (150 mg/kg intraperitoneally) as trial groups or to receive the same volume of physiological saline as controls. Having been received Cyclophosphamide 8 h, 24 h, 48 h and 72 h later, the mice were injected 99Tcm-HYNIC-AnnexinV by tail vein. Imaging results and radioactivity in tissues were obtained at 1 h post injection of molecular probe. 99Tcm-DTPA-HSA was used as a marker of tumor blood flow. All radioactivities in tissues results were analyzed by the statistic software of SPSS10.0.

Results: Cyclophosphamide treatment significantly increased the tumor uptake (percentage activity of injected dose per gram of tissue [%ID/g]) of 99Tcm-HYNIC-AnnexinV. The optimum imaging time after a single dose of chemotherapy could be considered at 72 h post injection (1.87 ± 0.58 %ID/g for treated 72 h mice tumor-bearing and 1.18 ± 0.128 %ID/g for controls, P<0.05). The ratio(5.83±0.80%ID/g) of tumor/muscle was higher than those of tumor/blood(1.03±0.26%ID/g) and controls, and there was significantly different(P<0.05). 99Tcm-DTPA-HSA uptake was not significantly different in the treated and untreated groups, which indicated the increased accumulation of 99Tcm-HYNIC-AnnexinV in the tumor is not attributable to changes in blood flow.

Conclusions: The present study shows that the radioactive uptake of cell apoptosis in mice tumor-bearing is significantly increased at 72 h after a single dose of Cyclophosphamide treatment. The current results suggest the potential utility of cell apoptosis imaging in vivo as a noninvasive means to assess tumor response after a single dose of chemotherapy.