Macromolecular MRI contrast agents based upon dendrimers obviate many deficiencies of serum albumin or linear polymer based MRI contrast agents. This is due to their preparation through an iterative synthesis methodology that promotes controlled size and shape of the dendrimer concomitantly generating the means for reproducible chemistry key to clinical translation. To create MRI contrast agents with dendrimers, the terminal primary amines of dendrimers are modified with chelated Gd(III) technology developed in the Chemistry Section. Historically, these reagents demonstrated a molar relaxivity 6 times that of Magnevist, the currently approved MRI contrast agent as reported in a seminal collaborative publication from the Chemistry Section. Macromolecular chelate conjugated dendrimer based Gd(III) MR contrast agents have been shown to be tunable by adjusting fundamental criteria: generation (MW & physical size), core elements (lipophilicity & charge), PEG conjugation (prolonging circulation minimizing non-specific organ uptake), lysine co-administration (assisting in renal clearance), and conjugation to targeting vectors (molecular targeting). Appending targeting vectors to dendrimer based agents provides molecularly targeted imaging agents. Incorporation of NIR optical imaging dye, SPECT or PET emitting radionuclides, provides for the creation of multi-modality dendrimer based imaging agents. However, no results are readily available on any studies from this project due to a lack of involved personnel combined with the anticipated retirement of Dr. Brechbiel and closure of the Chemistry Section, and as such this project will be terminated this year.
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