The imaging probe

The central part of the AFM is the imaging probe. Its size and sharpness are critical to the level of attainable image resolution, and to limit imaging artefacts the probe 

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Most disease-specific molecular and cellular processes involve low concentrations and have low capacities. Therefore, molecular imaging requires highly sensitive imaging modalities to detect and quantify the imaging probes as it is done with short-lived radioisotopes. Optical imaging and ultrasound are next in sensitivity. MRI would require too high contrast agent concentrations... 

Cell-internalization via receptors is the route of choice in a number of Nuclear Medicine assays. For MRI, the design of the Imaging Probe requires the attachment of one or more Gd(III)-chelates to the ligand molecule. Such structural modification may drastically affect the internalization process with respect to the mechanism occurring for the native ligand. 

In order to deal with a system whose structural characteristics were unaltered by the loading with Gd(III) chelates, we choose Apoferritin because it allows the Imaging Probes to be entrapped inside its inner cavity (60). The exterior of such Gd(III)-loaded Apoferritin is exactly the same as in the parent Ferritin and then, once administered intravenously, it is quickly cleared-up by the proper receptors on hepatocytes (172). The process of loading Apoferritin with [GdHPD03A(H20)] consists first of the dissociation of the protein into subunits at pH 2, followed by its reforming at pH 7, thereby trapping the solution components (e.g., [GdHPD03A(H20)])... 

The field of view for the ultrasound equipment is rather small, typically, not more than 20-30 cm and just a few centimeters at higher spatial resolution. Normally, a cross-sectional image in the plane of the imaging probe is obtained. Respectively, the operator must know where to place the transducer to locate the area of an expected lesion, as compared with a whole-body CT, the wide flat view of planar X-ray or MRI scans. 

Modern AFMs use piezoelectric transducers to either raster-scan the imaging probe across the stationary sample, or the sample with respect to a stationary probe. Certain crystals exhibit a property known as the piezoelectric effect. When compressed or stretched, a piezoelectric crystal will build up alternate charges on opposite faces. 

The selection of the mRNA segments (NA nt 625-640 Ml nt 526-550) targeted by the imaging probes was based on previous work, which demonstrated the accessibility and uniqueness within the cellular and viral transcriptome [10]. 

Soluri A, Scopinaro F, De Vincentis G, Varvarigou A, Scafe R, Massa R, Schillaci O, Spanu A, David V. Tc [13Leu] bombesin and a new gamma camera, the imaging probe, are able to guide mammotome breast biopsy. Anticancer Res 2003 23 2139-2142. 

Figure 18.9 Kinetics of F-COX-2 inhibitor. The imaging probe enters tissue via hydrophobic diffusion and binds to COX-2, which is overexpressed in cancer. The inserted image, obtained 25 50 min after tracer injection, demonstrates low Uver and lung background activity but moderate tracer accumulation in the skeleton, which is explained by late defluorination of the compound. Focally increased tracer activity in the left axilla is due to tracer contamination (arrow).

A linker is usually introduced between the imaging probe and the ligand, with the aim to preclude or rnitiitnize imwanted interferences between these two moieties. Linkers may act as a pharmacokinetic modifier and have a profound impact on the biodistribution of the whole molecule (Rufini, 2006 Schottelius, 2004). The most popular linkers are short amino... 

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