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Master's Dissertation
DOI
10.11606/D.85.2008.tde-21092011-102343
Document
Author
Full name
Renata Ferreira Costa
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Osso Júnior, João Alberto (President)
Martinelli, José Roberto
Moraes, Tatiana Lavinas de
Title in Portuguese
Desenvolvimento de métodos e preparação de microesferas de polímero e resinas marcadas com Hólmio-166
Keywords in Portuguese
hólmio-166
microesferas
radiofarmácia
Abstract in Portuguese
A expansão do desenvolvimento de radionuclídeos para uso em terapia de tumores, permite que técnicas de tratamento de tumores sejam mais seletivas e adequadas. Novos agentes têm como finalidade reduzir o tempo de tratamento e acelerar o tempo de recuperação de muitos pacientes. O principal objetivo deste trabalho é o desenvolvimento de microesferas de ácido lático e resina marcadas com Hólmio-166, para que se obtenha um radiofármaco que possa oferecer um tratamento localizado do tumor e, portanto para que se tenha a máxima irradiação do tumor e a diminuição dos efeitos de toxicidade nos tecidos adjacentes saudáveis. A metástase hepática é a principal causa de morte de pacientes com câncer de colo retal, para estes pacientes a resposta da quimioterapia e da radioterapia é baixa. Uma alternativa é a radioterapia interna seletiva utilizando microesferas marcadas com Hólmio-166, um emissor b (Emax=1,84 MeV), com um alcance máximo no tecido de 8,4mm e emissor de fótons (81 keV, 6,2%), apropriado para a aquisição de imagens. A produção de Hólmio-166 é possível no reator nuclear IEA-R1 (IPEN-CNEN/SP), um reator de pesquisa com baixo fluxo de nêutrons. O Hólmio tem uma abundância de 100% na natureza e seção de choque de 64 barns. Isso permite produzir uma atividade de 344mCi (~12GBq) (reator IEA-R1, 60 horas, 4,0x 1013n .s-1.cm-2), o suficiente para produção de doses terapêuticas. As resinas de troca catiônica, AG50W-X2, AG50W-X8, Amberlite, Sephadex e Sepharose, foram marcadas com 166Ho. Todas elas apresentaram um ótimo resultado de marcação. As resinas AG50W-X2, AG50W-X8, Amberlite e Sephadex não têm o tamanho de partícula ideal para terapia de tumores hepáticos, porém foi proposto que partículas com tamanho entre 100-450 m podem ser usadas no tratamento de tumores de cabeça e pescoço. A resina Sepharose tem as características essenciais para terapia de tumores hepáticos. Entretanto, estudos in vivo devem ser realizados para comprovar a sua eficácia. O preparo das microesferas de ácido lático não foi bem sucedido, mas a primeira fase da preparação apresentou bons resultados.
Title in English
Development of methods of preparation of polymer-based and resin-based microspheres labeled with holmium-166
Keywords in English
holmium-166
microspheres
radiopharmacy
Abstract in English
A surge in research activity is expanding the applications for therapeutic radiopharmaceuticals, which are employing more sophisticated targeting methodologies and more appropriate therapeutic isotopes for the tumors being treated. These new agents will reduce treatment time and accelerate recovery for many patients. The aim of this work is the development of resin-based and acid lacticbased microspheres labeled with 166Ho, in order to obtain selective delivery of radioisotopes to the tumor, thus maximizing the irradiation effect while sparing toxicity to the surrounding healthy liver. Liver metastases cause the majority of deaths from colorectal cancer, and response to chemotherapy and external radiotheraphy is poor. An alternative is an internal radionuclide therapy using microspheres labeled with 166Ho, a beta minus emitter (Emax=1.84 MeV), with maximum tissue range 8.4 mm, that also emits photons (81keV, 6.2%) suitable for imaging. The production of 166Ho is feasible in the IEA-R1 Reactor at IPEN-CNEN/SP, a low power reactor with low neutron fluxes. The nuclear reaction has a cross section of 64 barns and 165Ho has a natural abundance of 100%. It is possible to produce 344 mCi (~12GBq) (IEA-R1 Reactor, 60 hours, 4,0x 1013n .s-1.cm-2) a sufficient therapeutic dose, depending on the demand of doses. The cation exchange resins, AG50W-X2, AG50W-X8, Amberlite, Sephadex and Sepharose, were labeled with 166Ho. All the resins showed a very good retention. Although AG50W-X2, AG50W-X8, Amberlite and Sephadex did not have the right particle size, it is suggested that particles of 100-450 m could be used in the treatment of head-and-neck tumours. Sepharose labeled with 166Ho has essential characteristics for treatment liver therapy. However, further in vivo studies should be performed to prove its effectiveness. The preparation of acid lactic-based microspheres was not successful, but the first step of the preparation was very effective.
 
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Publishing Date
2011-10-17
 
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