""""""""Macromolecular agents composed of either serum albumins or linear polymers have MRI contrast enhancement factors less than those predicted for rigid molecules of comparable size, attributed to the flexibility and segmental motions within the polymer chain. To obviate this deficiency, MRI contrast agents have been developed based upon Starburst PAMAM dendrimers, wherein terminal primary amines are modified with chelating agents and then gadolinium complexes formed. Such constructs possess a molar relaxivity up to 6 times that of simple Gd-DTPA, currently employed in the clinic, and better than twice that of other macromolecular agents. Excellent conventional MR imaging and 3D time of flight MR angiograms have been obtained and studies have been expanded to thoroughly explore the utility of these agents and to determine the effects of dendrimer size (clearance and localization), the number of gadolinium complexes included within the construct (relaxivity and effects of charge), and toxicity. Ongoing experiments in a canine model system have already demonstrated outstanding detailed imaging of the vasculature and potential development as blood pool agents when using the G6 generation dendrimer construct. Due to results indicative of vasculature leakage of this particular reagent, this study has been modified and the G8 dendrimer is currently being evaluated for utility as an MRI contrast agent. A CT contrast agent based upon albumin conjugated to iopanoic is vcurrnetly being evaluated in pre-clinical models for use in quantitating flow and dispersion of therapeutics being injected inter-cranially. This material is being compared versus a comparable MRI albumin based reagent and preparations are underway to prepare the iodine based reagent for use in clinical trials. Use of dendrimers to augment the number of chelates conjugated to monoclonal antibodies, and then greatly increase both specific activity for therapeutic applications and radiolabeling efficiency, was examined. Exceptionally good non- specific targeting of radio-sensitive organs was promoted by the dendrimer itself and although this could be partially controlled by manipulation of charge through metal complex formation, this technology was deemed counter-productive and discontinued for this specific application.""""""""
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