Imaging Biomarkers and Computer-Aided Diagnosis Laboratory, Radiology and Imaging Sciences Department, Clinical Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1182, USA.
Mol Imaging. 2011 Aug;10(4):305-16. doi: 10.2310/7290.2010.00054. Epub 2011 Apr 26.
Mutated adenomatous polyposis coli (APC) genes predispose transformations to neoplasia, progressing to colorectal carcinoma. Early detection facilitates clinical management and therapy. Novel lectin-mediated polymerized targeted liposomes (Rh-I-UEA-1), with polyp specificity and incorporated imaging agents were fabricated to locate and image adenomatous polyps in APC(Min/+) mice. The biomarker α-L-fucose covalently joins the liposomal conjugated lectin Ulexeuropaeus agglutinin (UEA-1), via glycosidic linkage to the polyp mucin layer. Multispectral optical imaging (MSI) corroborated a global perspective of specific binding (rhodamine B 532 nm emission, 590-620 nm excitation) of targeted Rh-I-UEA-1 polymerized liposomes to polyps with 1.4-fold labeling efficiency. High-resolution coregistered optical coherence tomography (OCT) and fluorescence molecular imaging (FMI) reveal the spatial correlation of contrast distribution and tissue morphology. Freshly excised APC(Min) bowels were incubated with targeted liposomes (UEA-1 lectin), control liposomes (no lectin), or iohexol (Omnipaque) and imaged by the three techniques. Computed tomographic quantitative analyses did not confirm that targeted liposomes more strongly bound polyps than nontargeted liposomes or iohexol (Omnipaque) alone. OCT, with anatomic depth capabilities, along with the coregistered FMI, substantiated Rh-I-UEA-1 liposome binding along the mucinous polyp surface. UEA-1 lectin denotes α-l-fucose biomarker carbohydrate expression at the mucin glycoprotein layer; Rh-I-UEA-1 polymerized liposomes target and image adenomatous polyps in APC(Min) mice.
突变的腺瘤性结肠息肉病（APC）基因易导致肿瘤转化，进而发展为结直肠癌。早期检测有助于临床管理和治疗。新型凝集素介导的聚合靶向脂质体（Rh-I-UEA-1），具有息肉特异性，并结合了成像剂，用于定位和成像 APC（Min/+）小鼠中的腺瘤性息肉。生物标志物α-L-岩藻糖通过糖苷键与脂质体连接的凝集素槐凝集素（UEA-1）共价结合，连接到息肉粘蛋白层。多光谱光学成像（MSI）证实了靶向 Rh-I-UEA-1聚合脂质体与息肉的特异性结合（罗丹明 B 532nm 发射，590-620nm 激发）具有全局观点，靶向 Rh-I-UEA-1 聚合脂质体的标记效率为 1.4 倍。高分辨率共配准的光学相干断层扫描（OCT）和荧光分子成像（FMI）显示了对比分布和组织形态的空间相关性。将靶向脂质体（UEA-1 凝集素）、对照脂质体（无凝集素）或 iohexol（欧乃派克）与 APC（Min）肠道新鲜切除物孵育，并用三种技术进行成像。计算机断层定量分析并未证实靶向脂质体比非靶向脂质体或单独的 iohexol（欧乃派克）更强烈地结合息肉。OCT 具有解剖深度能力，与共配准的 FMI 一起，证实了 Rh-I-UEA-1 脂质体沿着粘蛋白息肉表面结合。UEA-1 凝集素表示粘蛋白糖蛋白层中α-L-岩藻糖生物标志物碳水化合物的表达；Rh-I-UEA-1 聚合脂质体靶向和成像 APC（Min）小鼠中的腺瘤性息肉。
