Nanopartícula de óxido de gadolínio amino-modificada utilizada como agente de contraste para imagens em ressonância magnética

Abstract

Introduction: Magnetic Resonance Imaging (MRI) is a propaedeutic modality that uses non-ionizing radiation for the acquisition of non-invasive medical images, useful in the diagnosis of various pathologies. To improve the sensitivity of MR, paramagnetic contrast media (MCs) are used, mainly gadolinium (Gd). Although widely used, MCs lack specificity for the diagnosis of different types neoplastic, for example. Objective: to analyze the in vitro and in vivo kinetic behavior of a novel nanoparticle of gadolinium oxide functionalized with an amino group (NP-Gd2O3:NH2) as a contrast agent for MRI. Materials and Methods: in vitro studies with Peripheral Blood Mononuclear Cells (PBMC) and endothelial cells were performed by stimulating them with NP-Gd2O3:NH2 and Gd-DOTA (gadolinic acid-tetraazacyclododecanotetra-acetic acid). Proinflammatory cytokines and apoptosis were quantified by ELISA and flow cytometry tests, respectively. Pre-clinical studies with Wistar rats (Rattus norvegicus) were also performed to compare the two contrasts using two doses of NP-Gd2O3:NH2 (1 mg / mL and 2 mg / mL) and Gd-DOTA (10 mg / mL). Results: análises in vitro com ambas doses de NP-Gd2O3:NH2 e Gd-DOTA indicaram ausência de toxicidade nas linhagens celulares e baixa toxicidade em PBMC. Ao analisar as medidas de intensidade de pixel (relacionada neste estudo à intensidade de sinal (IS)) em cada animal e órgão (cérebro, fígado, rim e baço), observaram-se hiporrealce da NP-Gd2O3:NH2 a 1 mg/mL em relação ao Gd-DOTA (controle), e hiperrealce da NP-Gd2O3:NH2 a 2 mg/mL em relação ao controle. Notaram-se, ainda, menor efeito da NP no rim, e contraste de longo prazo por mais de 24 horas. Conclusion: in summary, the new NP-Gd2O3:NH2, besides showing low toxicity and good biocompatibility, was also able to increase IS in several organs and with slow washing. The amino group bound to NP may allow the conjugation of specific probes for the monitoring of diseases and their treatments, giving it the potential to replace the conventional contrasts.