Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
J Control Release. 2011 Sep 25;154(3):298-305. doi: 10.1016/j.jconrel.2011.05.022. Epub 2011 May 27.
Targeting angiogenic vasculature has been validated as a viable approach for cancer imaging and therapy. The tumor vasculature-specific ligand asparagine-glycine-arginine (NGR) peptide targets the isoform of aminopeptidase N (APN, also referred to as CD13) that is expressed on the endothelial cells in angiogenic vessels such as the neovasculature in tumors. APN/CD13 has become widely recognized as a rational target for therapeutic development and several NGR-conjugated agents are now in pre-clinical and clinical development. In the current study, a CT image-based approach is used to evaluate the in vivo performance of several NGR conjugated liposome formulations that vary in terms of NGR density and PEG spacer arm length. Indeed, for the first time it is demonstrated that CT imaging can be used for quantitative and longitudinal assessment of the pharmacokinetics and biodistribution of an actively targeted liposome formulation containing an iodinated agent. In comparison to conventional methods, the CT image guided drug delivery approach enables visualization of the intratumoral distribution of liposomes and quantification of the fraction of tumor occupied by the vesicles over time. This study is the first to use CT for molecular imaging.
靶向血管生成已被证实是癌症成像和治疗的可行方法。肿瘤血管特异性配体天冬酰胺-甘氨酸-精氨酸（NGR）肽靶向在血管生成血管（如肿瘤中的新生血管）的内皮细胞上表达的氨肽酶 N（APN，也称为 CD13）的同种型。APN/CD13 已被广泛认为是治疗开发的合理靶点，并且现在有几种 NGR 缀合的药物正在临床前和临床开发中。在当前的研究中，使用基于 CT 图像的方法来评估几种 NGR 缀合脂质体制剂的体内性能，这些制剂在 NGR 密度和 PEG 间隔臂长度方面有所不同。事实上，这是首次证明 CT 成像可用于定量和纵向评估含有碘代试剂的主动靶向脂质体制剂的药代动力学和生物分布。与传统方法相比，CT 图像引导的药物输送方法能够可视化脂质体在肿瘤内的分布，并随时间定量评估由囊泡占据的肿瘤部分。这项研究首次使用 CT 进行分子成像。
