Protease activated receptor-1 targeted 99Tcm-(HYNIC-BMS-200261)(tricine)(TPPTS) imaging on nude mice bearing human breast cancer

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 values: 47.66, 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 values: 0.934 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. Key words: Breast neoplasms; Receptors, proteinase-activated; Antistatic agents; Radionuclide imaging; Tumor cells, cultured; Mice, nude