A Gadolinium Complex Confined in Silica Nanoparticles as a Highly Efficient T₁/T₂ MRI Contrast Agent

Abstract

MRI is a powerful, noninvasive diagnostic tool that provides high-resolution three-dimensional anatomical images of soft tissues consisting of 3D maps of longitudinal and transverse local proton relaxation rates R 1 = 1/T 1 and R 2 = 1/ T 2 . [1] However, due to the relatively low sensitivity of these rates to natural variation between the tissues, paramagnetic compounds are administered in up to 40 % of clinical MRI examinations to improve the image contrast. Such compounds, named contrast agents (CAs), act as enhancers of the R 1 and R 2 values in the tissues in which they distribute. The efficacy of a CA is measured by its relaxivities r 1 and r 2 defined as r a = (R a ÀR a0 )/[CA] (a = 1, 2), in which R a0 is the measured relaxation rate without the CA. The most common clinically approved CAs are monoaqua Gd III complexes that have r 1 values of about 4 s À1 mm À1 at the imaging field of 1.5 T. While obviously successful for basic anatomical applications, these relaxivities are not sufficient to enable many applications that might be envisaged, notably for molecular or functional imaging. Much effort has been invested in the past years to obtain contrast agents with higher relaxivity to image biological targets. [2] The standard relaxivity theory [1a, b, 3] provides a reasonable guide for optimization at imaging fields above 1 T. [4] It was recognized early on that high relaxivity in the range of 0.5-1.5 T can be achieved by optimizing the inner-sphere (IS) relaxivity mechanism, that is, by slowing down the tumbling of Gd

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