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Doctoral Thesis
DOI
10.11606/T.85.2014.tde-29102014-130657
Document
Author
Full name
Ana Claudia Machado Silva
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Mesquita, Carlos Henrique de (President)
Carneiro, Janete Cristina Gonçalves Gaburo
Chojniak, Rubens
Lima, Eduardo Nóbrega Pereira
Mastro, Nélida Lúcia Del
Title in Portuguese
Cinética e dosimetria do [177Lu-DOTA0, Tyr3]octreotato em pacientes com tumores carcinoides
Keywords in Portuguese
177Lu
análise compartimental
dosimetria
tumor carcinoide
Abstract in Portuguese
Tumores carcinoides (neoplasias bem diferenciadas) são tumores neuroendócrinos que podem surgir em diferentes locais anatômicos. Na população a prevalência dos tumores carcinoides é de aproximadamente 10 casos para um milhão de habitantes e sua incidência é maior na quinta e sexta década de vida. Este trabalho propõe um modelo cinético baseado na teoria da análise compartimental em humanos com tumores carcinoides que se submeterão ao tratamento com o radiofármaco [177Lu-DOTA0,Tyr3]Octreotato. Imagens cintilográficas dinâmicas planares, obtidas imediatamente à injeção de 370 MBq (10 mCi) do radiofármaco, foram obtidas com o tomógrafo SPECT (Single Photon Emission Computed Tomography). Por meio da seleção de regiões de interesse (ROI) os resultados foram digitalizados e aplicados ao modelo cinético aqui proposto. A primeira fase do estudo (atividade de 370 MBq) teve como objetivo conhecer os parâmetros cinéticos e subsequentemente, o paciente foi submetido ao protocolo de tratamento radioterápico, a critério médico, aos quatro ciclos de 7,4 GBq (200 mCi) do radiofármaco. Desta forma, foi possível estimar previamente as constantes cinéticas ki,j da biodistribuição do 177Lu-DOTATATO no corpo, sendo ki,j a fração de transferência do i-ésimo compartimento (tecido ou órgão) para o j-ésimo compartimento a partir das ROI demarcadoras dos órgãos de maior captação, a saber: fígado, rins, região vascularizada e tumores carcinoides. A partir das constantes cinéticas ki,j a estimativa de dose absorvida em 26 órgãos foi estimada pelo método MIRD. Os resultados dosimétricos foram compatíveis com outras metodologias descritas na literatura. Para um paciente adulto de 73,6 kg, em termos médios seus rins (sem os protetores renais) recebem a maior intensidade de dose (2,39 mGy/MBq) seguido do fígado (0,70 mGy/MBq). Observou-se que tumores com aproximadamente 100g recebem dose da ordem de 0,52 mGy/MBq independentemente da posição a que se encontram no corpo. Este achado se deve à predominância do dano devido às partículas beta quando comparado à radiação gama que possui pouco rendimento de emissão no processo de decaimento do 177Lu. Portanto, os parâmetros cinéticos que promovem a captação do 177Lu nas células são os principais responsáveis pela composição da dose no tumor e demais órgãos.
Title in English
Kinetic and dosimetry [177Lu-DOTA0 ,Tyr3]octreotate in patients with carcinoid tumors
Keywords in English
177Lu
carcinoid tumor
compartimental analysis
dosimetry
Abstract in English
Carcinoid tumors (well differentiated neoplasms) are neuroendocrine tumors that may arise in different anatomical locations. The population prevalence of carcinoid tumors is approximately 10 cases per one million inhabitants. Its incidence is higher in the fifth and sixth decade of life. This paper proposes a kinetic model in humans with carcinoid tumors who will underwent treatment with the radiopharmaceutical [177Lu-DOTA0,Tyr3 ]OCTREOTATE based on the theory of compartmental analysis. Dynamic planar scintigraphic images acquired immediately upon injection of 370 MBq (10 mCi) of the radiopharmaceutical were obtained with the SPECT (Single Photon Emission Computed Tomography) tomography. Samples from regions of interest (ROI) were used for the kinetic study applying the kinetic proposed model. The first phase of the study (activity 370 MBq) was aimed to evaluate the kinetic parameters. Subsequently, the patient underwent the [177Lu-DOTA0,Tyr3 ]OCTREOTATE radiotherapy protocol, under the physician's prescription (up to four cycles of 7.4 GBq (200 mCi)). Thus, it was possible to previously estimate the kinetic constants ki,j relative to biodistribution of [177Lu-DOTA0,Tyr3 ]OCTREOTATE in the body. The ki,j is the transfer fraction from the ith compartment (a tissue or an organ) to the jth compartment. Only few organs showed significant ROI radioactivity count level, among them: the liver, kidney, blood and carcinoid tumors. The MIRD method and the kinetic constants ki,j were used to estimate the absorbed dose in 26 body organs. The absorbed dose D(mGy/MBq) was comparable to other methods described in the literature. For an adult patient of 73.6 kg, on average, the kidneys (without amino acid protectors) showed the highest dose (2.39 mGy/MBq) followed by liver (0.70 mGy / MBq) and tumor (0.52 mGy/MBq) with a tissue size of approximately 100 g. It was observed that tumors receive the same absorbed dose D(mGy/MBq) regardless their position in the body. This finding is due to the predominance of the tissue radiation damage of beta particles compared to gamma radiation that has little yield emission in the 177Lu decay scheme. Therefore, the kinetic parameters ki,j that promote the uptake of 177Lu in cells are primarily responsible for the absorbed D dose in the tumor and other organs.
 
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Publishing Date
2014-11-07
 
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