title: Mono(pyridine-N-oxide) DOTA analog and its G1/G4-PAMAM dendrimer conjugates labeled with 177Lu: radiolabeling and biodistribution studies.
abstract: (177)Lu radiolabeling of the first (G1-) or fourth (G4-) generation polyaminoamide (PAMAM) dendrimer conjugates with DOTA-like bifunctional chelator with one methylenepyridine-N-oxide pendant arm (DO3A-py(NO-C)) stability of the radiolabeled species and their pharmacokinetic characteristics were evaluated in preclinical experiments. The results showed that the G1- and G4-dendrimer conjugates, modified in average with 7.5 or 57 DO3A-py(NO-C) chelating units, respectively, can also be labeled with (177)Lu with a high specific activity and radiochemical purity even at 37 °C. The radiolabeled species were stable for at least 24h. Distribution profile of G1-dendrimer conjugate in organs and tissues of rats was more favorable than that of G4 one. On the other hand, the later dendrimer conjugate bears a substantially higher number of metal chelators per molecule enabling binding of a considerably larger number of radiometals. Our results indicate that an employment of dendrimer-chelate conjugates with bound radiometals might represent a prospective way for radiolabeling of biologically active target-specific macromolecules to obtain markedly high specific activity.
authors: Department of Biophysics and Physical Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic. Electronic address: laznickova@faf.cuni.cz.
authors: A
authors: A
authors: Laznickova
authors: Department of Biophysics and Physical Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.
authors: V
authors: V
authors: Biricova
authors: Department of Pharmacology and Toxicology, Division of Radiopharmacy, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.
authors: M
authors: M
authors: Laznicek
authors: Department of Inorganic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 2030, 12840 Prague 2, Czech Republic.
authors: P
authors: P
authors: Hermann
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000737:chemistry; D050091:Dendrimers / Q000493:pharmacokinetics*; D006573:Heterocyclic Compounds, 1-Ring / Q000493:pharmacokinetics*; D007553:Isotope Labeling / Q000379:methods; D008187:Lutetium / Q000493:pharmacokinetics*; D008297:Male; D011725:Pyridines / Q000493:pharmacokinetics; D011868:Radioisotopes / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C520644:1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid; D002614:Chelating Agents; D050091:Dendrimers; D006573:Heterocyclic Compounds, 1-Ring; C104700:PAMAM Starburst; D011725:Pyridines; D011868:Radioisotopes; D008187:Lutetium; C013229:pyridine N-oxide
keywords: DOTA derivative; Dendrimer conjugates; Lutetium complexes; Macrocyclic ligands; Radiopharmaceuticals