Lipid nanodiscs (LNDs), comprising a phospholipid bilayer encircled by two molecules of a recombinant membrane scaffold protein, can be targeted to tumors with covalently attached antibodies (Abs) or their fragments. Antibody attachment to click chemistry based PEGylated lipids on LNDs including DOTA allowed PET imaging with the positron emitter 64Cu. Carcinoembryonic antigen (CEA) positive tumors in CEA transgenic mice were chosen as a tumor target. Fab' fragments, that otherwise are rapidly cleared by the kidney due to their small size, were retained in circulation when conjugated to LNDs. Untargeted PET imaging of 64Cu-DOTA-LNDs revealed low tumor uptake (4-5% ID/g) in the range expected for the enhanced permeability retention (EPR) effect with high liver uptake (17-21% ID/g) indicating gut clearance. Fab' targeted LNDs showed little improvement over untargeted LNDs, but intact IgG targeted LNDs gave high tumor uptake (40% ID/g) with low liver (8% ID/g), demonstrating that tumor targeting with antibody conjugated LNDs is feasible.

中文翻译：

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CEA 阳性肿瘤中 64Cu-DOTA-Anti-CEA 聚乙二醇化脂质纳米盘的抗体靶向 PET 成像。

脂质纳米圆盘 (LND) 包含由两个重组膜支架蛋白分子包围的磷脂双层，可通过共价结合抗体 (Ab) 或其片段靶向肿瘤。抗体连接到 LND 上基于点击化学的聚乙二醇化脂质（包括 DOTA）允许使用正电子发射器 64Cu 进行 PET 成像。选择CEA转基因小鼠中的癌胚抗原（CEA）阳性肿瘤作为肿瘤靶标。Fab' 片段由于体积小而被肾脏迅速清除，但在与 LND 结合时仍保留在循环中。64Cu-DOTA-LND 的非靶向 PET 成像显示低肿瘤摄取 (4-5% ID/g) 在预期的增强通透性保留 (EPR) 效应的范围内，高肝脏摄取 (17-21% ID/g) 表明肠道清除。棒棒哒