EVALUATION OF RADIOLABELED TPGS-BASED NANOMICELLES AS IMAGING PROBES. IN VIVO CHARACTERIZATION IN HEALTHY AND TUMOR BEARING ANIMALS.

TESAN, FIORELLA C.; GIAQUINTA DIEGO; NICOUD, MELISA B; MORETTON, MARCELA A.; MEDINA, VANINA A.; CHIAPPETTA, DIEGO A.; ZUBILLAGA, MARCELA; SALGUEIRO, MARÍA J.

Mar del Plata

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; 2016

Sociedad Argentina de Investigación Clínica

TPGS-based nanomicelles (TBN) is a system that has beenused for delivery of therapeutic drugs. The aim of this work is tolabel TBN with a gamma emitting nuclide as 99mTc and evaluateits potential use as an imaging probe for cancer diagnosis. Rad iolabellingof TBN with 99mTc was performed by the direct method.Radiochemical impurities (free 99mTc and radiocolloids) wereassessed by thin layer chromatography and filtration. Size andmorphology of radiolabeled nanomicelles were characterized bydynamic light scattering and by transmission electronic microscopyrespectively. Pharmacokinetic studies were performed in healthyanimals by two different assays: a 24h plasmatic concentrationcurve and biodistribution (BD) by means of small animal imaging(static and dynamic studies) after intravenous administration(1mCi/animal) of the radiolabeled probe. Regions of interest weredrawn over organs of interest in the static images acquired inorder to get semi quantitative results of the radioactive micellesBD. To evaluate the tumor uptake, two animal models of breastcáncer were used: N-nitroso-N-methyl-urea induced mammaryadenocarcinoma in Sprague Dawley rats and a syngeneic subcutaneoustumor (4T1 breast cell line) in balb-c mice. The uptakeratio (Tumor/Background) was calculated. Plasmatic concentrationover time in healthy animals resulted in a two phase decay curve(R2=0.85;%ID0=41.46; Pl=1.984; Kfast=2.052h-1; Kslow=0.3379h-1).%Total activity in BD studies for 1 and 12 hs post injection were:6.1±0.5; 3.9±0.1 soft tissue, 1.2±0.2; 1±0.1 bone, 1.5±0.6; 0.7±0.3heart, 16.6±1.3; 26.5±1.7 kidneys, 8.6±1.1; 11.1±0.1 liver. T/B wasbetween 30 and 80 in the images performed in the chemicallyinduced tumors. However no uptake was appreciated in imagesof the 4T1 tumors in mice. Further studies must be conducted toestablish the quantity of TBN to be administered for in vivo protocols.Animal procedures were approved by the CICUAL of theFFYB, UBA (Res CD 3761/13).