Nonuniformly Distributed Targets

The sensitivity of the imaging probe may be limited when sparse epitopes are not distributed uniformly in the voxel. This situation may be met when the target molecules are on the endothelial wall. The decrease of sensitivity relies on the limited walking path of the water molecule during the acquisition protocol, for which a given voxel does not appear as a hyperintense spot in a Trweighted image if the contrast agent is not uniformly distributed, i.e., if it is confined only in a small region of the acquired voxel. Recently, Morawski et al. reported an interesting experiment that appears to rule out this issue [73]. They succeeded in the MRI visualization of a single cell layer exposing, on their outer surface, epitopes at approximately 102 pM concentration by anchoring to each target site, an imaging probe containing approximately 105 Gd-chelates. At 1.5 T, the relaxivity of the imaging probe was 17.9 ± 0.6 s" 1mM_ 1 when referred to Gd(III) unit, and 1.69 X 106 ± 6 X 104 s" 'mM"1 when referred to the concentration of the whole probe. With the use of a standard 3D imaging technique, they were able to observe substantial contrast between the voxels containing the labeled cell monolayer and the corresponding voxels containing unlabeled cells. From their results the authors concluded that: (1) picomolar binding is sufficient to achieve diagnostic contrast to noise level if high payload particles are employed; (2) sparse molecular epitopes, such as tissue factors, can be imaged on cells at clinical field strengths under certain reasonable conditions; and (3) model-based predictions of the local concentrations of targeted paramagnetic agents are accurate if the fundamental characteristics of the agents are known.

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Number of Gd/cell

FIGURE 4.9 Longitudinal relaxation rate (1/Tj) measured at 20 MHz and 25°C of cell pellets labeled with Gd-HPDO3A by pinocytosis or by electroporation.

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Number of Gd/cell

FIGURE 4.9 Longitudinal relaxation rate (1/Tj) measured at 20 MHz and 25°C of cell pellets labeled with Gd-HPDO3A by pinocytosis or by electroporation.

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