^99mTc-TP5-3 Micro SPECT/CT For The Early Evaluation Of Response In Mice Bearing MDA-MB-231 Breast Carcinoma After A Single Dose Of Paclitaxel Chemotherapy

Objects To synthesize 99mTc-TP5-3 and evaluate it’s biodistribution and kinetics as a molecular probe for the detection apoptosis, and evaluate tumor apoptosis after a single dose of paclitaxel chemotherapy in MDA-MB-231 breast tumor model. Methods TP5-3 was labeled with 99mTc using directly, then analyzed with HPLC (Integral LC system 100). The radioactivity in tissues were measured and expressed on %ID/g(percentage activity of injection dose per gram of tissue) and T/NT(region of tumor/region of muscle). The mice were divided into two groups, the treatment group were receive a single dose of paclitaxel (40mg/kg,tain vein) and the control group were receive the same volume of normal saline. After therapy, 99mTc-TP5-3 was injected by tail vein in these two groups. Micro-SPECT/CT was performed at 2h postinjection. Radioactivity in different tissues was determined after imaging. Apoptotic cells were measured with flow cytometry. The morphological changes of the apoptotic cells were observed by light microscopies. The data in this study were analyzed by the statistic software of SPSS 19.0.Results The radiochemical purity of 99mTc-TP5-3 was> 95%. The predominant uptake was found in kidney, rapid clearance was observed in the blood and kidney, the uptake of liver was relatively low. The ratio of tumor to muscle(T/NT) in treated group was 4.21±0.06, significantly higher than that of control group (1.57±0.67).(p<0.05,). Compared with the retention percentages of radioactivity(%ID/g) in tumor tissue at 48 hours later, the radioactivity of tumor tissue in treatment group is higher than that in control group[%ID/g of treatment group is 4.82±0.54,%ID/g of control group is 1.44±0.38]. In comparison with activity [(13.74±4.21)%ID/g] at 5 min postinjection,85% of initial activity reduced in blood at 3 hours [(2.07±0.35)%ID/g]. The tumor uptake of 99mTc-TP5-3 of treatment group correlated well with apoptotic cells (r2=0.971,p=0.00030.05. Histopathology further confirmed a large number of apoptosis was occurred in the tumor after paclitaxel treatment.Conclusion 99mTc-TP5-3 appeared to be a potential and useful molecular probe of tumor cell apoptosis.