Dendrimer‐based metal chelates: A new class of magnetic resonance imaging contrast agents

Wiener, Erik C.; Brechbiel, Martin W.; Brothers, H.; Magin, Richard L.; Gansow, Otto A.; Tomalia, D. A.; Lauterbur, Paul C.

doi:10.1002/mrm.1910310102

Cited by 670 publications

(489 citation statements)

References 27 publications

(23 reference statements)

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“…It has been shown that, at the imaging fields, high relaxivities can be obtained in the presence of long reorientational times ( R ) of the complex. The molecular motion of the complex can be slowed down by the formation of covalent or non-covalent conjugates between the paramagnetic complex and a slowly moving substrate, such as proteins (4), mi-celles (5), polyaminoacids (6), polysaccharides (7), or dendrimers (8).…”

Section: Rational Design Of Gd(iii)-based Systems Endowed With High Rmentioning

confidence: 99%

Insights into the use of paramagnetic Gd(III) complexes in MR‐molecular imaging investigations

Aime

Cabella

Colombatto³

et al. 2002

Magnetic Resonance Imaging

327

275

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Can gadolinium III [Gd(III)] complexes be considered good candidates for magnetic resonance (MR)-molecular imaging studies? In this review article, we examine the principal issues that are the basis of successful use of Gd-based protocols in molecular imaging applications. High relaxivity is the primary requisite. Therefore, the design of such paramagnetic probes has to be pursued keeping in mind the relationships between structure, dynamics, and the relevant parameters involved in paramagnetic relaxation processes. Moreover, the limited number of target molecules on cellular membranes makes it necessary to define strategies aimed at delivering many Gd-containing moieties to the sites of interest. Examples are reported for the attainment of very high relaxivities for the design of new routes for pursuing the accumulation of small sized Gd(III) complexes at the targeting sites. An efficient cellular uptake of Gd-containing probes is the key step for attaining the visualization of targeted cells by MR imaging, and selected examples are reported. In this context, the problem of the assessment of the minimum amount of Gd(III) complexes necessary for the MR imaging-visualization of cells has been addressed by reporting the authors' observations on the cell-internalization of Gd(III) complexes. A particularly efficient delivery system is represented by Gd-loaded apoferritin, which allows the MR visualization of hepatocytes when the number of Gd-complexes per cell is 4 Ϯ 1 ϫ 10 7 . Finally, the potential of responsive systems is considered by outlining the exploitation of the amplification effect brought about by the action of a specific enzymatic activity on the relaxivity of a suitably functionalized Gd(III) complex. IT IS NOW WELL ESTABLISHED that magnetic resonance imaging (MRI) is the pre-eminent methodology among the various diagnostic modalities currently available, as it offers a powerful way to map structure and function in soft tissues by sampling the amount, flow, and environment of water protons in vivo. The intrinsic contrast can be augmented by the use of contrast agents (CA) in both clinical and experimental settings. Thus, the use of CA adds highly relevant physiological information to the superb anatomical resolution obtained in MR images. Most of the work with CAs has dealt with the use of gadolinium (III) [Gd(III)] complexes, because this metal ion couples a large magnetic moment with a long electron spin relaxation time.The new scenery of molecular imaging applications requires the development of a novel class of CAs characterized by a higher contrasting ability and improved targeting capabilities (1). In this survey, we intend to tackle some basic issues that are of fundamental importance for the use of Gd(III)-based systems in molecular imaging applications, namely: 1) actual understanding of the determinants of T 1 -relaxivity of Gd(III) complexes, and how to proceed to attain very high relaxivities; 2) how one may envisage efficient routes for the delivery of a high number of Gd(III) complexes a...

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Section: Rational Design Of Gd(iii)-based Systems Endowed With High Rmentioning

confidence: 99%

Insights into the use of paramagnetic Gd(III) complexes in MR‐molecular imaging investigations

Aime

Cabella

Colombatto³

et al. 2002

Magnetic Resonance Imaging

327

275

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“…In 1994, Lauterbur and co-workers [53] pioneered the first study on dendrimer-based MRI agents. In that study, the DTPA chelating agent was conjugated to the terminal amine of PAMAM dendrimers of generations 2 and 6, followed by complexing with GdCl 3 to deliver the dendrimer contrast agent 1 (Fig.…”

Section: Mri Contrast Agents Based On Dendrimer Nanotechnologymentioning

confidence: 99%

Dendrimer-based magnetic resonance imaging agents for brain cancer

et al. 2018

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Brain cancer is one of the most lethal and difficult-to-treat cancers because of its physical location and biological barriers. The mainstay of brain cancer treatment is surgical resection, which demands precise imaging for tumor localization and delineation. Thanks to advances in bioimaging, brain cancer can be detected earlier and resected more reliably. Magnetic resonance imaging (MRI) is the most common and preferred method to delineate brain cancer, and a contrast agent is often required to enhance imaging contrast. Dendrimers, a special family of synthetic macromolecules, constitute a particularly appealing platform for constructing MRI contrast agents by virtue of their well-defined three-dimensional structure, tunable nanosize and abundant surface terminals, which allow the accommodation of high payloads and numerous functionalities. Tuning the dendrimer size, branching and surface composition in conjunction with conjugation of MRI functionalities and targeting moieties can alter the relaxivity for MRI, overcome the blood-brain barrier and enhance tumor-specific targeting, hence improving the imaging quality and safety profile for precise and accurate imaging of brain tumors. This short review highlights the recent progress, opportunities and challenges in developing dendrimer-based MRI contrast agents for brain tumor imaging.

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“…Major applications are related to the drug delivery systems development (Gillies, Fréchet, 2005;Medina, El-Sayed, 2009;Nanjwade et al, 2009;Wijagkanalan, Kawakami, Hashida, 2011;, solubility (Devarakonda, Hill, Villiers, 2004) and biocompatibility improvements (reduce toxicity) (Duncan, Izzo, 2005;Sadekar, Ghandehari, 2010;Ciolkowski et al, 2012), magnetic resonance image (MRI) contrast (Wiener et al, 1994;Margerum et al, 1997;Kobayashi et al, 2003;Kojima et al, 2011;Tang et al, 2012), targeted drug delivery (Yang et al, 2009;Menjoge et al, 2011) and gene delivery (Dufès, Uchegbu, Schätzlein, 2005;Kim et al, 2007;Mintzer, Simanek, 2009;Shcharbin, Klajnert, Bryszewska, 2009;Nam et al, 2012).…”

Section: Dendrimers As a Platform For No Transportmentioning

confidence: 99%

Nitric oxide releasing-dendrimers: an overview

Roveda

Franco

2013

Braz. J. Pharm. Sci.

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Platforms able to storage, release or scavenge NO in a controlled and specific manner is interesting for biological applications. Among the possible matrices for these purposes, dendrimers are excellent candidates for that. These molecules have been used as drug delivery systems and exhibit interesting properties, like the possibility to perform chemical modifications on dendrimers surface, the capacity of storage high concentrations of compounds of interest in the same molecule and the ability to improve the solubility and the biocompatibility of the compounds bonded to it. This review emphasizes the recent progress in the development and in the biological applications of different NO-releasing dendrimers and the nitric oxide release pathways in these compounds.

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Dendrimer‐based metal chelates: A new class of magnetic resonance imaging contrast agents

Cited by 670 publications

References 27 publications

Insights into the use of paramagnetic Gd(III) complexes in MR‐molecular imaging investigations

Insights into the use of paramagnetic Gd(III) complexes in MR‐molecular imaging investigations

Dendrimer-based magnetic resonance imaging agents for brain cancer

Nitric oxide releasing-dendrimers: an overview

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