title: Synthesis, Radiolabeling, and In Vivo Imaging of PEGylated High-Generation Polyester Dendrimers.
abstract: 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-ene 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 ± 2.1 nm. This PEGylated dendrimer was subsequently radiolabeled using [(99m)Tc(CO)3(H2O)3](+) 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.
authors: Department of Chemistry and Chemical Biology, McMaster University , Hamilton, Ontario L8S 4M1, Canada.
authors: Stuart A
authors: SA
authors: McNelles
authors: Department of Chemistry and Chemical Biology, McMaster University , Hamilton, Ontario L8S 4M1, Canada.
authors: Spencer D
authors: SD
authors: Knight
authors: Department of Chemistry and Chemical Biology, McMaster University , Hamilton, Ontario L8S 4M1, Canada.
authors: Nancy
authors: N
authors: Janzen
authors: Department of Chemistry and Chemical Biology, McMaster University , Hamilton, Ontario L8S 4M1, Canada.
authors: John F
authors: JF
authors: Valliant
authors: Department of Chemistry and Chemical Biology, McMaster University , Hamilton, Ontario L8S 4M1, Canada.
authors: Alex
authors: A
authors: Adronov
mesh_terms: D000818:Animals; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D007553:Isotope Labeling; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy*; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011859:Radiography; D051381:Rats; D013667:Technetium / Q000737:chemistry / Q000494:pharmacology; D015899:Tomography, Emission-Computed, Single-Photon; D023041:Xenograft Model Antitumor Assays
chemical_list: D050091:Dendrimers; D011091:Polyesters; D011092:Polyethylene Glycols; D013667:Technetium; C000595209:polyethylene glycol 1000