Glycoconjugate probes and targets for molecular imaging using magnetic resonance

Abstract

Review Molecular recognition of sugar residues applied in molecular imagingMolecular imaging aims at probing the molecular abnormalities that are the basis of diseases rather than to image their effects [1]. An important prerequisite of this approach is the selection of appropriate markers of disease and of targeting vectors to recognize them. The latter can include low-molecular weight substrates for enzymes or high-molecular weight affinity ligands, such as monoclonal antibodies, hormone analogs and recombinant proteins. Of the three major classes of biomolecules (proteins, nucleic acids and carbohydrates), the latter class is the least exploited in molecular imaging. However, a dense layer of glyco conjugates covers all cells and carbohydrate mediated cellular recognition plays an important role in nature, both in normal and malignant processes, such as cell-cell communication, infection, inflammation, metastasis and reproduction. As carriers of information, the carbohydrates have far greater potential than proteins and nucleic acids; three different nucleotides or amino acids can generate only six distinguishable structures, while over 1000 structures can be built up from three different monosaccharides [2]. This level of complexity is probably the reason for the fact that the exploration of these compounds in molecular imaging is lagging behind [3]. Recently, significant progress has been made in glycochemistry and glycobiology; for example, automated solid-phase synthesis of oligo saccharides has become possible [4], carbohydrate-based vaccines have been developed [5] and high-throughput methods have been designed for the screening of molecular interactions [6]. The exciting new developments in glycoscience are opening way for new challenges in exploring the full potential of carbohydrates in molecular imaging. Therefore, here we give an overview of the recent literature on the use of glycoconjugates either as probes or targets in molecular imaging using MRI.MRI contrast agents (CAs) are broadly described as positive or negative, depending on whether they give rise to a brightening or a darkening effect on the MR image, respectively. The positive or brightening effect predominantly relates to the longitudinal proton relaxation time (T 1 ) and the negative or darkening effect predominantly relates to the transverse proton relaxation time (T 2 ). To date, the majority of commercially available and clinically applied positive CAs are Gd 3+ complexes of the polyaminocarboxylates diethylene triamine pentacetic acid (DTPA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) (see FiguRe 1 for some typical examples) and negative CAs are various iron oxide particles. These agents are not actively targeting. The targeted CAs for application in molecular imaging that are currently under development and described below are generally based on compounds 1 (Gd-DTPA) and 2 (Gd-DOTA), as well as iron oxide nanoparticles.Glycoconjugate probes and targets for molecular imaging using magnetic resonanceRecently...

Cyclometalated Iridium(III) Bipyridine–Phenylboronic Acid Complexes as Bioimaging Reagents and Luminescent Probes for Sialic Acids

“…The log K b values for the binding of Neu5Ac range from 3.61 to 3.85 and are larger than those of d ‐glucose (from 1.68 to 2.92), d ‐galactose (from 2.63 to 3.17), and d ‐mannose (from 2.16 to 3.34). These values follow the order: Neu5Ac> d ‐galactose≈ d ‐mannose> d ‐glucose, which is in accord with those reported in related studies ,,,. Variation of the cyclometalating ligands did not substantially change the binding affinity of the complexes to Neu5Ac and the other three sugars.…”

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“…The same authors also prepared the similar 11 C‐based glycoconjugate 29 (Figure 8) but found that these two PET tracers were not suitable as LacZ reporter probes 50. Related LacZ reporter molecules have been developed as MRI probes and are reviewed elsewhere 9…”

“…In glycobiology, MRI has found its main application in the preparation of probes based on galactosides, glucuronides, or larger glycoconjugates (Figure 1). An interesting review has been published recently,9 so carbohydrate‐based compounds developed as MRI probes are not covered here.…”

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