Investigação de cimentos radioativos de Y-90 e Ho-166 para tratamentos de metástases ósseas por carcinomas de mama

Abstract

The present thesis has aboard Radiovertebroplasty. The work’s objective was to broaden the studies of the materials involved in the technique, and the dosimetric response under simulated conditions. The in situ composite radiological response and toxicity analysis were also evaluated. The biomaterial, said radioactive bone cement, was prepared by PMMA (Polymethylmethacrylate) and Hydroxyapatite (HAp). The concentrations and proportion of the compounds have important physicochemical properties to optimize the treatment. The PMMA is a hydrophobic polymer with low porosity compared to trabecular bone tissue. The thermal profile studied showed an exothermic phase of more than 60 °C which could produce cellular necrosis. It was also observed that if the PMMA applied in a trabecular implant, due to its poor porosity, could prevent the diffusion of cells of the bone marrow reducing the processes of the cellular dynamics and frequent adhesion by the osteoblastic and osteoclastic cells in the microenvironment. Such conditions led to the analysis of materials with different concentrations in HAp, incorporated into the bone cement. The biomaterial was composed from five different concentration ratios of the HAp+PMMA system. In the case the HAp was added to PMMA as a (1-x)PMMA-xHAp stoichiometric function in such a way that in a 1:1 ratio the exothermic phase of the cementitious material was reduced to room temperature. Thermal analysis studies (DSC and TGA) confirmed the existence of a reversible glass transition around 103 °C. On the other hand, subsequent to this transition occur degradation phenomena releasing CO2 and H2O in the polymer segments. This degradation contributes macroscopically to the increased porosity on material. The mechanical study results showed an inversely proportional relationship between the increase of the HAp concentration and the decrease of the compressive strength modulus. Another finding was the proximity in the compressive strength of the block polymerized cementitious material to the compressive strength values of the highly porous trabecular bone. In addition, it was possible to conclude that this increase of HAp added the porosity of the bone implant, theoretically due to the segregation reactions on water molecules trapped in the HAp and exposed to PMMA at the mixing time to all components. The radionuclides studied to compose the cement were Ho-166, Y-90 and Sm-153 due to the emission of energetic beta particles, with reduced half-life, and natural abundance of the isotope, the cost-benefit ratio of their production. Computational simulations on vertebral models with bone metastases showed a better spatial distribution of the absorbed dose of Y-90 compared to the other radionuclides reaching more than 90% of the volume of metastasis with a deposited dose of 65 Gy. However, Ho-166 also met the therapeutic proposal of Radiovertebroplasty. Quantitative radiological contrast studies showed a differentiated radiological response of the composite in implants in vertebrae, indicating the possible reduction or elimination in the use for contrast agents such as barium sulphate (BaSO4) in a 1:1 blend of cementitious material. Cold cytotoxicity tests with radioactive bone cement showed monocyte adhesion in culture medium and biocompatibility for material conferring other studies that show a relationship between the activation of monocytes in macrophages and their phagocytic function for PMMA particles smaller until 10 μm, indicating a possible bioceramic signaling for osteoclast reabsorption.