Kang H W, Weissleder R, Bogdanov A
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Amino Acids. 2002;23(1-3):301-8. doi: 10.1007/s00726-001-0142-2.
Targeted diagnostic agents are expected to have a significant impact in molecular imaging of cell-surface associated markers of proliferation, inflammation and angiogenesis. In this communication, we describe a new class of targeted polyamino acid-based protected graft copolymers (PGC) of poly-(L-lysine) and methyl poly-(ethylene glycol) (PGC) covalently conjugated with a monoclonal antibody fragment, F(ab')(2). We utilized targeted PGC conjugates as carriers of near-infrared indocyanine fluorophores (Cy5.5) for optical imaging of endothelial cell populations expressing IL-1 beta inducible proinflammatory marker E-selectin. We compared two conjugation chemistries, involving either introduction of sulfhydryl group to F(ab')(2), or via direct attachment of the antibody fragment directly to the chemically activated PGC. Both PGC-based targeted agents demonstrated high binding specificity (20-30 fold over non-specific uptake) and were utilized for imaging E-selectin expression on human endothelial cells activated with IL-1 beta.
靶向诊断试剂有望在细胞表面相关的增殖、炎症和血管生成标志物的分子成像中产生重大影响。在本通讯中，我们描述了一类新型的基于聚氨基酸的受保护接枝共聚物（PGC），它由聚（L-赖氨酸）和聚乙二醇甲基醚（PGC）与单克隆抗体片段F(ab')(2)共价连接而成。我们利用靶向PGC偶联物作为近红外吲哚菁荧光团（Cy5.5）的载体，对表达白细胞介素-1β诱导的促炎标志物E-选择素的内皮细胞群体进行光学成像。我们比较了两种偶联化学方法，一种是将巯基引入F(ab')(2)，另一种是通过将抗体片段直接连接到化学活化的PGC上。两种基于PGC的靶向试剂均表现出高结合特异性（比非特异性摄取高20-30倍），并用于成像用白细胞介素-1β激活的人内皮细胞上的E-选择素表达。
