The overall purpose was to improve the tumor targeting properties of radiolabeled biologicals by optimizing chemical parameters. This years research was centered on 2 projects. The first project was to modify a spherical polymer, generation 3 PAMAM dendrimer (G3, MW 6909) and use it as a universal carrier of radiolabels and biological molecules. Using 3-[I-125]iodobenzoate and norbiotinamidosuccinate as model molecules, we have optimized the conjugation level of these molecules to G3 and improved the whole-body clearance kinetics in mice by blocking the non-specific uptake of G3 to liver and kidney upon neutralization of the highly positive-charged G3 by succinylation. We further improved the clearance kinetics of the radiolabel by inserting a metabolizable linker, triglycine between the label and G3 to a level that can be useful for a therapy approach. This approach can be applied to synthesize At-211 labeled G3-biotin for an alpha emitter-therapy of cancer that is pretargeted with antibody-streptavidin. The second project was to label Annexin V (AV) with I-125, In-111, Y-86, and Tc-99m for the detection of apoptosis to monitor the progress of cancer therapy. Among these, Tc-99m and Y-86 labeled AV were of particular interest because of their ideal imaging properties.
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