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.
Subject(s)
Dendrimers/pharmacokinetics , Fluorescein-5-isothiocyanate/pharmacokinetics , Melanoma, Experimental/diagnostic imaging , Molecular Imaging/methods , Organotechnetium Compounds/pharmacokinetics , Polyamines/pharmacokinetics , Radiopharmaceuticals/pharmacokinetics , Animals , Dendrimers/administration & dosage , Fluorescein-5-isothiocyanate/administration & dosage , Mice , Mice, Inbred C57BL , Organotechnetium Compounds/administration & dosage , Polyamines/administration & dosage , Radionuclide Imaging , Radiopharmaceuticals/administration & dosage , Time Factors , Tissue DistributionABSTRACT
Anti-CD20 (Rituximab®), a specific chimeric monoclonal antibody used in CD20-positive Non-Hodgkin's Lymphoma, was conjugated to a bifunctional quelate (DOTA) and radiolabeled with (177)Lu through a simple method. [(177)Lu]-DOTA-anti-CD20 was obtained with a radiochemical purity higher than 97%, and showed good chemical and biological stability, maintaining its biospecificity to CD20 antigens. Monte Carlo simulation showed high doses deposited on a spheroid tumor mass model. This method seems to be an appropriate alternative for the production of [(177)Lu]-DOTA-anti-CD20 as therapeutic radiopharmaceutical.
