Responsive Imaging Probes

For Gdin-based agents, the relaxivity response is most often related to a change in water accessibility or to the variation of the size and consequently of the rotational correlation time of the complex. In addition to Gdm complexes, PARACEST agents are 

In the field of responsive agents, enzyme targeting has specific advantages. A small concentration of the enzyme can convert a relatively high amount of the probe in multiple catalytic cycles which considerably decreases the detection limit for the enzyme as compared to other biomolecules. Moreover, enzymatic reactions are usually highly specific therefore, the observed change 

Beside changes in the rotational correlation time, modifications in the hydration state of the chelate were also used to follow enzymatic activity. Gd(HP-D03A)-derivative complexes bearing a galactopyranose moiety were studied as reporters for 

PARACEST agents with a response to enzymatic activity have also been reported. Pagel et al. used a Tm1 DOTA monoamide complex containing a peptide chain which is hydrolyzed by the Caspase-3 enzyme (204,205). Following enzymatic cleavage, the PARACEST effect originating from the amide proton disappears due to the hydrolysis of the amide bond. 

Targeted enzyme p galactosidase peptidase esterase, lipase sulfa tase reductase 

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PARACEST agents are particularly well adapted for the development of responsive probes, since the rate of exchange and the chemical shift of the protons leading to a PARACEST effect depend on various physico-chemical parameters. We will discuss several examples from this field in the following section on Responsive Imaging Probes. ... 

Far-red to near infrared analyte-responsive fluorescent probes based on organic fluorophore platforms for fluorescence imaging 13CSR 622. 

This is the first example of electrochemical tuning of lanthanide luminescence and opens up new opportunities for signal manipulation and responsive imaging [60]. The seven-coordinate lanthanide complex with an appended carboxylate-containing arm (Fig. 9.23) has been used as pH responsive probe through change in the molecular structure in solution. An increase in pH deprotonates the carboxylic moiety that in turn binds to the unsaturated lanthanide. This affords dimeric entities in solution where the displacement of solvent molecules triggers an increase in emission intensity proportional to pH [65]. 

Fig. 23 (a) DNAzyme-based sensor design with two dabcyl quenchers and a FAM fluorophore (top) and mechanism of operation (bottom), (b) Fluorescence response before and after complete cleavage through Pb2+ inset contains the corresponding image of the DNAzyme probe in the absence (left) and presence of Pb2+ (after 2 min of reaction time, right). (Reprinted with permission from [150]. Copyright 2003 American Chemical Society)... 

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