Therefore, there are strict constrains on the inner structure and coating of MPIO to allow their accumulation at concentrations high enough to be detected by MRI. Notably, MPIO are rapidly eliminated from the circulation by the reticuloendothelial system, thereby limiting their ability to reach their target ( 15). We and others demonstrated the applicability of targeted MPIO for molecular MRI in several experimental models, including cardiovascular ( 9, 10) and neurovascular disorders ( 11), autoimmune diseases ( 12, 13), and cancer ( 14). MPIO display a higher sensitivity than USPIO thanks to higher iron content ( 8). More recently, microparticles of iron oxide (MPIO) with diameters close to 1 μm have been used as a new family of contrast agent for molecular MRI ( 7). However, the low sensitivity (due to the small amount of iron payload per particle), poor specificity (due to passive extravasation through permeated endothelial barriers), and long delay between administration and imaging (up to 24 hours after intravenous injection) have precluded the use of USPIO as targeted molecular imaging agents ( 6). USPIO can be conjugated to targeting moieties such as peptides or antibodies and have a favorable safety profile in humans. To date, nanosized contrast agents such as ultrasmall particles of iron oxide (USPIO) with a diameter ranging from 10 to 50 nm have been the primary focus of molecular MRI studies ( 5). Amplification strategies aiming at binding a large amount of contrast material to the molecular target are thus necessary. Magnetic resonance spectroscopy and deuterium metabolic imaging allow quantitative mapping of the in vivo dynamics of cellular metabolism but are not available for all molecular targets ( 4). The usual concentration of relevant targets for molecular imaging is around 10 −9 to 10 −12 M in human tissues, whereas MRI detects clinically approved gadolinium chelate at concentrations over 10 −6 M ( 2, 3).
Magnetic resonance imaging (MRI) is a promising modality for molecular imaging but remains limited by low sensitivity ( 1). The high payload of superparamagnetic material, excellent toxicity profile, short circulation half-life, and widespread reactivity of the M3P particles provides a promising platform for clinical translation of immuno-MRI. After conjugation to monoclonal antibodies, targeted M3P display high sensitivity and specificity to detect inflammation in vivo in the brain, kidneys, and intestinal mucosa. The resulting biodegradable microprobes (M3P for microsized matrix-based magnetic particles) carry up to 40,000 times higher amounts of superparamagnetic material than classically used nanoparticles while preserving favorable biocompatibility and excellent water dispersibility. Here, we synthetized a contrast agent for molecular MRI based on a previously unknown mechanism of self-assembly of catechol-coated magnetite nanocrystals into microsized matrix-based particles. However, the low intrinsic sensitivity of MRI to detect exogenous contrast agents and the lack of biodegradable microprobes have prevented its clinical development. Molecular magnetic resonance imaging (MRI) holds great promise for diagnosis and therapeutic monitoring in a wide range of diseases.
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