Reporter Protein-Targeted Probes for Magnetic Resonance Imaging

Abstract

Contrast agents for magnetic resonance imaging are frequently employed as experimental and clinical probes. Drawbacks include low signal sensitivity, fast clearance and non-specificity that limit efficacy in experimental imaging. In order to create a bio-responsive MR contrast agent, a series of four Gd(III) complexes targeted to the HaloTag reporter were designed and synthesized. HaloTag is unique among reporter proteins for its specificity, versatility, and the covalent interaction between substrate and protein. In similar systems, these properties produce prolonged in vivo lifetimes and extended imaging opportunities for contrast agents, longer rotational correlation times, and increases in relaxivity (r1) upon binding to the HaloTag protein. In this work we report a new MR contrast probe, 2CHTGd, which forms a covalent bond with a target protein and results in a dramatic increase in sensitivity. A 6-fold increase in r1, from 3.8 mM−1s−1 to 22 mM−1s−1, is observed upon 2CHTGd binding to the target protein. This probe was designed for use with the HaloTag protein system which allows for a variety of substrates (specific for MRI, florescence, or protein purification applications) to be used with the same reporter.

Enhancing T 1 magnetic resonance imaging contrast with internalized gadolinium(III) in a multilayer nanoparticle

“…We can infer from this increased relaxivity that the presence of PEG molecules on the surface of the nanoparticles facilitates the approach of water protons to the NM surface, closer to the internally encapsulated Gd(III) ions, and reduces the mobility of the nanocomplex. The diffusion of water in the proximity of the Gd(III) is known to play an important role in the enhancement of proton relaxivity (19,29,(41)(42)(43). Besides Gd(III) concentration and surface functionalization, temperature can also affect the relaxivity, which can have a major impact in vivo (33).…”

High Relaxivity Gd(III)–DNA Gold Nanostars: Investigation of Shape Effects on Proton Relaxation

“…36 Although second- and outer-sphere contributions to relaxivity are generally considered insignificant due to the high rate of water diffusion past the Gd(III), this phenomenon is sometimes cited to explain unexpectedly high values of r 1 in nanoconjugate systems. 6,19,30,37,38 …”

Dynamic cyclen–metal complexes for molecular sensing and chirality signaling

“…10), this reagent showed drastically improved relaxivity in MRI analyses. 42 The coordinated water molecules on the Gd 3+ center and their exchanges with bulk water molecules are essential for the Fig. 8 Heptadentate cyclen-lanthanide complexes as anion receptors.…”