title: Synthesis, radiolabeling, and bio-imaging of high-generation polyester dendrimers.
abstract: A series of aliphatic polyester dendrons, generations 1 through 8, were prepared with a core p-toluenesulfonyl ethyl (TSe) ester as an easily removable protecting group that can be efficiently replaced with a variety of nucleophiles. Using amidation chemistry, a tridentate bis(pyridyl)amine ligand which is known to form stable complexes with both Tc(I) and Re(I) was introduced at the dendrimer core. Metalation of the core ligand with (99m)Tc was accomplished for generations 5 through 7, and resulted in regioselective radiolabeling of the dendrimers. The distribution of the radiolabeled dendrimers was evaluated in healthy adult Copenhagen rats using dynamic small-animal single photon emission computed tomography (SPECT). The labeled dendrimers were cleanly and rapidly eliminated from the bloodstream via the kidneys with negligible nonspecific binding to organs or tissues being observed. These data were corroborated by a quantitative biodistribution study on the generation 7 dendrimer following necropsy. The quantitative biodistribution results were in excellent agreement with the data obtained from the dynamic SPECT images.
authors.affiliation: Department of Chemistry, McMaster University, Hamilton, Ontario L8S 4M1, Canada.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Parrott
authors.forename: S Rahima
authors.initials: SR
authors.lastname: Benhabbour
authors.forename: Chantal
authors.initials: C
authors.lastname: Saab
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Lemon
authors.forename: Shannon
authors.initials: S
authors.lastname: Parker
authors.forename: John F
authors.initials: JF
authors.lastname: Valliant
authors.forename: Alex
authors.initials: A
authors.lastname: Adronov
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011422:Propionates / Q000737:chemistry; D051381:Rats; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D050091:Dendrimers; D015609:Organotechnetium Compounds; D011091:Polyesters; D011422:Propionates; D015082:2,2'-Dipyridyl; D013667:Technetium; C048062:2,2'-dipyridylamine