• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Doctoral Thesis
DOI
https://doi.org/10.11606/T.85.2011.tde-29062011-164358
Document
Author
Full name
Eutimio Gustavo Fernández Núñez
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2011
Supervisor
Committee
Faintuch, Bluma Linkowski (President)
Marumo, Maria Helena Bellini
Moro, Ana Maria
Nascimento, Nanci do
Oliveira Filho, Renato Santos de
Title in Portuguese
Desenvolvimento de conjugados de dextran manose radiomarcados para detecção de linfonodo sentinela
Keywords in Portuguese
câncer
dextran
linfonodo sentinela
radiofármaco
tecnécio-99m
Abstract in Portuguese
O diagnóstico precoce de tumores e metástase constitui atualmente o elemento de maior impacto dentro das políticas de saúde públicas contra o câncer. No câncer de mama e melanoma, a técnica de biópsia de linfonodo sentinela, para o diagnostico de metástase, tem sido muito utilizada evitando a dissecção total dos nodos da região anatômica afetada, e permitindo definir com precisão o procedimento terapêutico a utilizar. O objetivo principal deste trabalho centrou-se no desenvolvimento de conjugados radiomarcados de dextran-manose para diagnóstico, utilizando o núcleo de tecnécio altamente estável, [99mTc(CO)3]+. A cisteína, ligante tridentado, foi incorporada na estrutura dos conjugados, como agente quelante do Tecnécio-99m. As condições de marcação definidas para os produtos avaliados garantiram altos valores de pureza radioquímica (>90%) e atividade específica (>59,9 MBq/nmol) assim como uma alta estabilidade in vitro. Os conjugados de dextran-cisteína-manose demonstraram uma captação superior (4 vezes maior) nos nodos linfáticos em relação aos homólogos que não possuíam manose na estrutura. O conjugado de dextran-cisteína-manose de 30 kDa radiomarcado (99mTc-DCM2) foi o traçador com melhor desempenho biológico entre os avaliados à diferentes atividades injetadas. Demonstrou-se que concentrações superiores a 1 M favorecem a retenção do produto nos nodos linfáticos. As comparações com radiofármacos já utilizados no Brasil (Dextran-500 e Fitato) para detecção de linfonodo sentinela evidenciaram a superioridade do 99mTc-DCM2.
Title in English
Development of radiolabled mannose-dextran conjugates for sentinel lymph node detection
Keywords in English
cancer
dextran
sentinel lymph
Abstract in English
Early diagnosis of tumors and metastasis is the current cornerstone in public health policies directed towards the fights against cancer. In breast cancer and melanoma, the sentinel lymph node biopsy has been widely used for diagnoses of metastasis. The minor impact in patient of this technique compared with total nodes dissection and the accurate definition of therapeutic strategies have powered its spreading. The aim of this work was the development of radiolabeled dextran-mannose conjugates for diagnosis using the stable technetium core [99mTc(CO)3]+. Cysteine, a trident ligand, was attached to the conjugates backbone, as a chelate for 99mTc labeling. Radiolabeling conditions established for all products considered in this study showed high radiochemical purities (> 90%) and specific activities (>59,9 MBq/nmol) as well and high stability obtained through in vitro tests. The lymphatic node uptake increased significantly (4-folds) when mannose units were added to the conjugates compared with those without this monosaccharide. The radiolabeled cysteine-mannose-dextran conjugate with 30 kDa (99mTc-DCM2) showed the best performance at different injected activities among the studied tracers. Concentrations of this radiocomplex higher than 1 M demonstrated an improvement of lymph node uptakes. Comparisons of 99mTc-DCM2 performance with commercial radiopharmaceuticals in Brazil market for lymph node detection showed its upper profile.
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
Publishing Date
2011-08-01
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
CeTI-SC/STI
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2024. All rights reserved.