Synthesis, Radiolabeling, and In Vivo Imaging of PEGylated High-Generation Polyester Dendrimers

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• 作者：Stuart A. McNelles ; Spencer D. Knight ; Nancy Janzen ; John F. Valliant ; Alex Adronov
• 刊名：Biomacromolecules
• 出版年：2015
• 出版时间：September 14, 2015
• 年：2015
• 卷：16
• 期：9
• 页码：3033-3041
• 全文大小：708K
• ISSN：1526-4602

文摘

A fifth generation aliphatic polyester dendrimer was functionalized with vinyl groups at the periphery and a dipicolylamine Tc(I) chelate at the core. This structure was PEGylated with three different molecular weight mPEGs (mPEG₁₆₀, mPEG₃₅₀, and mPEG₇₅₀) using thiol鈥揺ne click chemistry. The size of the resulting macromolecules was evaluated using dynamic light scattering, and it was found that the dendrimer functionalized with mPEG₇₅₀ was molecularly dispersed in water, exhibiting a hydrodynamic diameter of 9.2 卤 2.1 nm. This PEGylated dendrimer was subsequently radiolabeled using [p>99mp>Tc(CO)₃(H₂O)₃]p>+p> and purified to high (>99%) radiochemical purity. Imaging studies were initially performed on healthy rats to allow comparison to previous Tc-labeled dendrimers and then on xenograft murine tumor models, which collectively showed that the dendrimers circulated in the blood for an extended period of time (up to 24 h). Furthermore, the radiolabeled dendrimer accumulated in H520 xenograft tumors, which could be visualized by single-photon emission computed tomography (SPECT). The reported PEGylated aliphatic polyester dendrimers represent a new platform for developing tumor-targeted molecular imaging probes and therapeutics.