Deane Natasha G, Manning H Charles, Foutch A Coe, Washington M Kay, Aronow Bruce J, Bornhop Darryl J, Coffey Robert J
Department of Surgery and Division of Surgical Oncology, Vanderbilt University, Nashville, TN 37235, USA.
Mol Cancer Res. 2007 Apr;5(4):341-9. doi: 10.1158/1541-7786.MCR-06-0225.
The peripheral benzodiazepine receptor (PBR) is a trans-mitochondrial membrane protein that modulates steroid biosynthesis. Recently, up-regulation and nuclear localization of PBR has been shown to be associated with colon, prostate, and breast cancer. PBR has been targeted by the exogenous synthetic ligand, PK11195, for various purposes including imaging. To capitalize on these observations, we developed a high-throughput, noninvasive, in vivo imaging approach to detect spontaneously arising colonic tumors in mice using a novel PBR-targeted molecular imaging agent (NIR-conPK11195). NIR-conPK11195 localized and was retained in colonic adenomas and carcinomas in Smad3(-/-) mice but not in non-neoplastic hamartomas or chronically inflamed colonic tissue. Using a fluorescence signal-to-noise ratio of > or =4-fold 13 h after injection of the agent, we detected colonic tumors with a sensitivity of 67% and a specificity of 86% in a cohort of 37 Smad3(-/-) mice and control littermates. Furthermore, using oral administration of dextran sulfate to induce colonic inflammation, we showed that the clearance profile of NIR-conPK11195 distinguished transient uptake in inflammatory tissue from longer term retention in tumors. Taken together, these results indicate that NIR-conPK11195 is a promising optical molecular imaging tool to rapidly screen for colonic tumors in mice and to discriminate inflammation from cancer.
外周苯二氮䓬受体（PBR）是一种跨线粒体外膜蛋白，可调节类固醇生物合成。最近研究表明，PBR的上调和核定位与结肠癌、前列腺癌和乳腺癌相关。PBR已被外源性合成配体PK11195靶向用于包括成像在内的各种目的。为利用这些观察结果，我们开发了一种高通量、非侵入性的体内成像方法，使用新型PBR靶向分子成像剂（NIR-conPK11195）检测小鼠自发产生的结肠肿瘤。NIR-conPK11195在Smad3（-/-）小鼠的结肠腺瘤和癌中定位并保留，但在非肿瘤性错构瘤或慢性炎症性结肠组织中则不然。在注射该试剂13小时后，使用荧光信噪比≥4倍，我们在一组37只Smad3（-/-）小鼠和对照同窝小鼠中检测结肠肿瘤的灵敏度为67%，特异性为86%。此外，通过口服硫酸葡聚糖诱导结肠炎症，我们发现NIR-conPK11195的清除曲线可区分炎症组织中的短暂摄取和肿瘤中的长期保留。综上所述，这些结果表明NIR-conPK11195是一种有前景的光学分子成像工具，可快速筛查小鼠结肠肿瘤并区分炎症与癌症。
