title: Development of 99mTc(CO)₃-dendrimer-FITC for cancer imaging.
abstract: Study of fluorophore and technetium labeling of poly(amido)-amine (PAMAM) generation 4 (G4) dendrimer and its evaluation as potential molecular imaging agent in both normal and melanoma-bearing mice, are described. Dendrimers were first conjugated with FITC (fluorescein isothiocyanate). Dendrimer-FITC was then incubated with the intermediate [(99m)Tc(CO)(3)(H(2)O)(3)](+) and purified by gel filtration. Biodistribution and scintigraphy images were performed administrating (99m)Tc(CO)(3)-dendrimer-FITC to normal mice (NM) or melanoma-bearing mice (MBM). Cryostat tissue sections from MBM mice were analyzed by confocal microscopy. Radiolabeling yield of dendrimer was approx. 90%. The (99m)Tc(CO)(3)-dendrimer-FITC complex was stable for at least 24h. Biodistribution studies in NM showed blood clearance with hepatic and renal depuration. MBM showed a similar pattern of biodistribution with high tumor uptake that allowed tumor imaging. Confocal microscopy analysis showed cytoplasmic distribution of (99m)Tc(CO)(3)-dendrimer-FITC.
authors.affiliation: Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de República, Mataojo 2055, 11400 Montevideo, Uruguay.
authors.forename: Marcos R
authors.initials: MR
authors.lastname: Tassano
authors.forename: Paola F
authors.initials: PF
authors.lastname: Audicio
authors.forename: Juan P
authors.initials: JP
authors.lastname: Gambini
authors.forename: Marcelo
authors.initials: M
authors.lastname: Fernandez
authors.forename: Juan P
authors.initials: JP
authors.lastname: Damian
authors.forename: Maria
authors.initials: M
authors.lastname: Moreno
authors.forename: Jose A
authors.initials: JA
authors.lastname: Chabalgoity
authors.forename: Omar
authors.initials: O
authors.lastname: Alonso
authors.forename: Juan C
authors.initials: JC
authors.lastname: Benech
authors.forename: Pablo
authors.initials: P
authors.lastname: Cabral
mesh_terms: D000818:Animals; D050091:Dendrimers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging*; D051379:Mice; D008810:Mice, Inbred C57BL; D057054:Molecular Imaging / Q000379:methods*; D015609:Organotechnetium Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011073:Polyamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D050091:Dendrimers; D015609:Organotechnetium Compounds; C531249:Poly(amidoamine); D011073:Polyamines; D019275:Radiopharmaceuticals; D016650:Fluorescein-5-isothiocyanate