Evaluation of Radiolabeled TPGS-based Nanomicelles as Imaging probes. In vivo characterization in healthy and tumor bearing animals.

TESAN F.; GIAQUINTA D.; NICOUD M.; MORETTON M.A.; MEDINA V.; CHIAPPETTA D.A.; ZUBILLAGA M.; SALGUEIRO J.

Mar del Plata

Encuentro; VII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE NANOMEDICINA (NANOMEDAR); 2016

TPGS-based nanomicelles (TBN) is a system that has been used for delivery of therapeutic drugs. The aim of this work is to label TBN with a gamma emitting nuclide as 99mTc and evaluate its potential use as an imaging probe for cancer diagnosis.Radiolabelling of TBN with 99mTc was performed by the direct method. Radiochemical impurities (free 99mTc and radiocolloids) were assessed by thin layer chromatography and filtration. Size and morphology of radiolabeled nanomicelles were characterized by dynamic light scattering and by transmission electronic microscopy respectively. Pharmacokinetic studies were performed in healthy animals by two different assays: a 24h plasmatic concentration curve 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 were drawn over organs of interest in the static images acquired in order to get semi quantitative results of the radioactive micelles BD. To evaluate the tumor uptake, two animal models of breast cancer were used: N-nitroso-N-methyl-urea induced mammary adenocarcinoma in Sprague Dawley rats and a syngeneic subcutaneous tumor (4T1 breast cell line) in balb-c mice. The uptake ratio (Tumor/Background) was calculated.Plasmatic concentration over 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±0.3 heart, 16.6±1.3; 26.5±1.7 kidneys, 8.6±1.1; 11.1±0.1 liver. T/B was between 30 and 80 in the images performed in the chemically induced tumors. However no uptake was appreciated in images of the 4T1 tumors in mice. Further studies must be conducted to establish the quantity of TBN to be administered for in vivo protocols.