99Tcm-TP5-3 microSPECT/CT for the early evaluation of response in mice bearing MDA-MB-231 breast carcinoma after a single dose of paclitaxel chemotherapy / 中华核医学与分子影像杂志

ABSTRACT

Objective To synthesize 99Tcm-TP5-3 and evaluate its biodistribution and kinetics as a molecular probe for the detection of 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 99Tcm directly,and analyzed with HPLC.The radioactivity in tissues was measured and expressed as ％ID/g and T/NT (tumor/muscle).The mice bearing MDA-MB-231 breast tumor were divided into two groupsthe treatment group which was given a single dose of paclitaxel (40 mg· kg-1,via tail vein),and the control group which was injected with the same volume of normal saline.After therapy,99Tcm-TP5-3 was injected via tail vein in both groups (100 μ1 for each mouse).MicroSPECT/CT was performed at 3 h 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.One-way analysis of variance,two-sample t test and linear correlation analysis were used to analyze the data.Results The radiolabeling efficiency was ＞ 95％ and the radiochemical purity of 99Tcm-TP5-3 was (96.0± 1.5)％ at room temperature for 4 h.The predominant uptake was found in the kidneys at 30 min postinjection ((8.48± 1.07) ％ID/g),with rapid tracer clearance from the circulation.By comparison with activity at 5 min postinjection ((13.74± 4.21) ％ID/g),85％ of the initial activity reduced in blood at 4 h ((2.07±0.35) ％ID/g; F=11.310,P＜ 0.05).99Tcm-TP5-3 was mainly accumulated in the kidneys,liver and stomach,and excreted via the kidneys.T/NT in the treated group was 4.21±0.06,which was significantly higher than that of the control group (1.57±0.67; t =12.820,P＜0.05).The radioactivity of tumor tissue in the treatment group was much higher than that in the control group (4.82±0.54) ％ID/g vs (1.44±0.38) ％ID/g,t=0.679,P＜0.05).The tumor uptake of 99Tcm-TP5-3 in the treatment group positively correlated well with the apoptotic cells (r =0.985,P＜0.05).Histopathology further confirmed that a large number of apoptosis had occurred in the tumor after paclitaxel treatment.Conclusion 99Tcm-TP5-3 appears to have potential to be a useful molecular probe for imaging tumor cell apoptosis.