Full text
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| Author(s): |
Adriano Radin
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2010-08-02 |
| Examining board members: |
Carlos Alberto Buchpiguel;
Elaine Bortoleti de Araújo;
Bronislaw Polakiewicz
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| Advisor: | Carlos Alberto Buchpiguel |
| Abstract | |
Over least 15 years the complex [[99mTc](H2O)3(CO)3]+ has been used as an intermediary to obtain technetium radiopharmaceuticals for applications in cardiology, neurology and oncology. Two important characteristics of this molecule are the easily that compound is obtained from aqueous solutions and the ease of substitution of H2O molecules by atoms of other ligand molecules. In this project we prepared new complexes [[99mTc](CMNS001-3)(H2O)(CO)3]+, where (CMNS001) = N-[(4-methoxy) benzyl]-1,2-diaminoethane, (CMNS003) = N,N\'- bis-[(4-methoxy)benzyl]-1,2-diaminoethane, and assessed the uptake of these complexes in murine melanoma cancer cell B16F10 and breast cells MCF-7 and MDA-MD-231, and compared with [[99m](MIBI)6]+ uptake. In vitro uptake for both new technetium complex reached values close to 5%, for all cell lines, whereas the [[99mTc](MIBI)6]+ uptake was close to 1 %. The assessment of subcellular distribution showed high accumulation of the new complex in the membrane fraction, for MDAMB- 231, while for B16F10 accumulation occurred both in membrane and cytoplasm; the concentration of [[99mTc](MIBI)6]+ was mainly in the cytoplasm portion. Biodistribution study in mice allowed to observe the capture of up to 1.6% of the administered dose per gram of tumor tissue for the complex [[99mTc](CMNS001)(H2O)(CO)3]+, whereas other organs such as heart, lung and muscle, showed uptake of about 5.6%, 6.4% and 2%, respectively. The complexes in this work showed a high rate of uptake in vitro, but was not reproduced in vivo model, which can be related to low concentration of the complexes inside the cells and reduced vascularity of tumor tissue, with lower intake of complex through the blood system. (AU) | |