title: Radiolabeling of PAMAM dendrimers conjugated to a pyridine-N-oxide DOTA analog with ¹¹¹In: Optimization of reaction conditions and biodistribution.
abstract: Polyamidoamine dendrimers (PAMAMs) of generations 1 (G1) and 4 (G4) were conjugated with a bifunctional pyridine-N-oxide DOTA analog, 10-[(4-carboxy-1-oxidopyridin-2-yl)methyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (H(4)do3a-py(NO-C)), through the pyridine-4-carboxylic acid group, and the conjugates were radiolabeled with indium-111. Reaction conditions for the radiolabelling were optimized. Both radiolabeled conjugates, G1-[(111)In(do3a-py(NO-C))] and G4-[(111)In(do3a-py(NO-C))], were kinetically stable for at least 48h after preparation; in the presence of competitive ligands, the radiochemical purity of the conjugates slightly decreased (4-7%) over the same time period. The preclinical pharmacokinetics of both agents were evaluated. Biodistribution and elimination in rats were more favorable for the G1-[(111)In(do3a-py(NO-C))] conjugate than G4-[(111)In(do3a-py(NO-C))] conjugate. However, the G1-[(111)In(do3a-py(NO-C))] conjugate was rapidly eliminated from the body, mainly through urine, while, significant and long-term radioactivity uptake in the liver and kidney was observed for the G4-[(111)In(do3a-py(NO-C))] conjugate.
authors.affiliation: Charles University in Prague, Faculty of Pharmacy, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. biricv@yahoo.co.uk
authors.forename: Veronika
authors.initials: V
authors.lastname: Biricová
authors.forename: Alice
authors.initials: A
authors.lastname: Lázničková
authors.forename: Milan
authors.initials: M
authors.lastname: Lázníček
authors.forename: Miloslav
authors.initials: M
authors.lastname: Polášek
authors.forename: Petr
authors.initials: P
authors.lastname: Hermann
mesh_terms: D000818:Animals; D050091:Dendrimers / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry* / Q000493:pharmacokinetics; D007205:Indium Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods*; D008297:Male; D011725:Pyridines / Q000737:chemistry* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: C520644:1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid; D050091:Dendrimers; D004337:Drug Carriers; D006573:Heterocyclic Compounds, 1-Ring; D007205:Indium Radioisotopes; C104700:PAMAM Starburst; D011725:Pyridines; D019275:Radiopharmaceuticals; C013229:pyridine N-oxide