Protease activated receptor-1 targeted 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) imaging on nude mice bearing human breast cancer / 中华核医学与分子影像杂志

ABSTRACT

Objective To study the reliability of 99Tcm-(hydrazinonicotinamide (HYNIC)-BMS-200261) (tricine) (trisodium triphenylphosphine-3,3',3"-trisulfonate (TPPTS)) as a radiotracer for protease activated receptor-1 (PAR-1) expression in breast cancer.Methods Fifteen nude mice bearing MDA-MB-435,MDA-MB-231 and MCF-7 human breast cancer xenografts (5 mice for each cell line) with different PAR-1 expression were used for 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) γ imaging,and tumor/non-tumor (T/NT) ratios were obtained with region of interest (ROI) technique.Afterwards,the biodistribution of 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) was analyzed in tumor-bearing nude mice,and the radioactivity in tumor (percentage activity of injection dose per gram of tissue,％ID/g) was calculated.The immunostaining was performed to examine PAR-1 expression in tumor tissue and semi-quantitative analysis was used.One-way analysis of variance and Pearson correlation analysis were used to analyze data.Results At 2 h postinjection,the T/NT ratios were 3.03±0.32,2.27±0.25 and 1.51±0.13 respectively in nude mice bearing MDA-MB-435,MDA-MB-231 and MCF-7 xenografts;the tumor uptakes of 99Tcm-(HYNIC-BMS-200261)(tricine)(TPPTS) were (1.03±0.15),(0.56±0.14) and (0.30±0.06) ％ID/g;PAR-1 expression levels were (17.22±2.71) ％,(10.78± 1.95) ％ and (2.80± 1.18) ％,respectively (F values47.66,46.36,62.35,all P＜0.05).The T/NT ratios and tumor uptake of 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) at 2 h post-injection were correlated with PAR-1 expression (r values0.934 and 0.929,both P＜0.05).Conclusions 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) imaging could be a noninvasive and effective method for monitoring PAR-1 expression in human breast cancer.