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WIREs Nanomed Nanobiotechnol
Impact Factor: 6.14

Revisiting an old friend: manganese‐based MRI contrast agents

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Abstract Non‐invasive cellular and molecular imaging techniques are emerging as a multidisciplinary field that offers promise in understanding the components, processes, dynamics and therapies of disease at a molecular level. Magnetic resonance imaging (MRI) is an attractive technique due to the absence of radiation and high spatial resolution which makes it advantageous over techniques involving radioisotopes. Typically paramagnetic and superparamagnetic metals are used as contrast materials for MR based techniques. Gadolinium has been the predominant paramagnetic contrast metal until the discovery and association of the metal with nephrogenic systemic fibrosis (NSF) in some patients with severe renal or kidney disease. Manganese was one of the earliest reported examples of paramagnetic contrast material for MRI because of its efficient positive contrast enhancement. In this review manganese based contrast agent approaches will be presented with a particular emphasis on nanoparticulate agents. We have discussed both classically used small molecule based blood pool contrast agents and recently developed innovative nanoparticle‐based strategies highlighting a number of successful molecular imaging examples. WIREs Nanomed Nanobiotechnol 2011 3 162–173 DOI: 10.1002/wnan.116 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vitro Nanoparticle-Based Sensing Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

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Publication trend from Scopus: surge in publication related to Gd and NSF.

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Preparation and characterization of manganese nanocolloids: Reaction conditions: (A) Preparation of ManOC and ManOL. (i)–(ii) sodium oleate, reflux, stirring; (iii)–(iv) 1‐octadecene, 325°C/70 min, stirring; (v) suspended with vegetable oil (2 w/v%), vortex, mixing; evaporation of chloroform under reduced pressure, 45°C; (vi) thin film formation from phospholipids mixture; (vii) homogenization, 20,000 psi, 4 min, 0°C; (viii) Mn‐oleate, suspended with sorbitan sesquioleate (>2 w/v%), vortex, mixing, evaporation of chloroform under reduced pressure, 45°C; then steps (vi), followed by (vii). (B) MRI images of fibrin‐targeted nanocolloids: (a) ManOC; (b) ConNC; (c) nontargeted‐ManOL and (d) ManOL, bound to cylindrical plasma clots measured at 3 T (pixel dimension: 0.73 mm × 0.73 mm × 5 mm slice thickness). (C) MR characterization of ManOC and ManOL in suspension: (top) ionic R1 and (bottom) R2 relaxivity. The measured R1 relaxation rate at 3 T for ManOC (circles) and ManOL (diamonds) as a function of manganese concentration. (Reproduced with permission from Ref 38. Copyright 2009 American Chemical Society).

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Preparation and characterization of manganese nanobialys: (Top left) TEM (drop deposited over nickel grid, 1% uranyl acetate) and (top right) atomic force microscope (AFM) image of nanobialys (drop deposited over glass) Reaction conditions: (1) anhydrous chloroform, gentle vortexing, room temperature; (2) aqueous solution of 2 [Mn(III)‐protoporphyrin], inversion, room temperature, filter using short bed of sodium sulfate and cotton; (3) Biotin‐Caproyl‐PE, filter mixed organic solution using cotton bed, 0.2 µM water, vortex, gently evaporation of chloroform at 45°C, 420 mbar, 0.2 µM water, sonic bath, 50°C, 1/2 h, dialysis (2 kDa MWCO cellulose membrane) against water. (Bottom) MRI images of fibrin‐targeted nanobialys (right) or control nanoparticles (bottom left) and (bottom middle) bound to cylindrical plasma clots measured at 3 T.

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Surface attached manganese‐oxo clusters improve MR contrast (PS: polystyrene beads).

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Example of convertible inorganic contrast agents.

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Structures of polycarboxylates and porphyrins used as ligands for manganese.

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Manganese‐based contrast agent families. Inset: Structure of dipyridoxal diphosphate (DPDP), the clinically approved manganese (II) agent for hepatobiliary imaging.

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Diagnostic Tools > In Vitro Nanoparticle-Based Sensing
Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
Therapeutic Approaches and Drug Discovery > Emerging Technologies

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