J Exp Ther Oncol.：分子探针为乳腺癌基因描绘“显像图”

近日，黑龙江省哈尔滨医科大学附属第四医院核医学科赵长久、付鹏等人在国家自然科学基金支持下，成功建立了一种快速、准确、及时、无创性地评价乳腺癌小鼠双微体扩增基因（MDM2）表达程度的影像学方法，使乳腺癌在分子水平发生改变的“早早期”被诊断成为可能。此项成果日前刊发于《美国核医学》杂志。

有文献报道，癌基因MDM2在鼠和人的很多组织中都有表达，被证实是一种癌基因，与多种肿瘤的发生、发展、转移、复发、放化疗抵抗等有关联。因此，在乳腺癌病人放化疗之前，及时、准确评价MDM2表达程度，对临床上制定医疗方案尤为重要。

赵长久教授课题组将小鼠MDM2作为研究靶点，利用“反义技术”合成了针对恶性肿瘤特异性极强的新型影像分子探针。通过一系列体外、体内研究，该研究组证实分子探针在体内外生物学特性稳定，在乳腺癌细胞内有较大摄取比率，在乳腺癌小鼠体内肿瘤区有较多分布。研究结果表明，MDM2分子探针能在乳腺癌小鼠身上进行分子成像，获得MDM2在肿瘤区分布的优质图像，且能在活体内无创伤性地定性、定量评价乳腺癌组织MDM2的表达程度。

The effect of Tc-99m-labeled MDM2 antisense oligonucleotide on gene expression in human breast cancer MCF-7 cells.
Abstract
To investigate the effect of radiolabed mouse double minute 2 (MDM2) antisense oligonucleotide on gene expression in human breast cancer MCF-7 cells, an antisense oligonucleotide (ASON) targeting MDM2 mRNA was synthesized and radiolabeled with 99Tcm. The labeling efficiency, radiochemical purity, and the ability of labeled ASON to hybridize to the sense oligonucleotides (SON) were investigated. To study whether the antisense probe hybridizes to respective sequence on MDM2 mRNA strand after radiolabeling, cells were incubated with radiolabeling oligonucleotides antisense oligonucleotide (0, 100, 500 nm/L) or mismatch oligonucleotide (ASONM) (500 nm/L) for 24 h, in the presence of Lipofectin 2000. RT-PCR and Western blotting was carried out to measure the MDM2 mRNA and protein levels. The antisense oligonucleotide was radiolabeled with the bifunctional chelator HYNIC at the labeling efficiency of 57.2 +/- 2.98% (n = 5) and the mismatch oligonucleotide was 56.3 +/- 3.01% (n = 5). The radiochemical purity was above 95% and labeled antisense oligonucleotide has the ability to hybridize to the sense oligonucleotide. The levels of mRNA and protein have significant differences in different concentration groups. The oligonucleotide can be successfully radiolabeled, and specially hybridized to the MDM2 mRNA and inhibit gene expression intensively as compared to mismatch oligonucleotide. This method will be very useful in the in vivo investigation of tumor targeting.