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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIASC010051-22
Application #
9556777
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
22
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Clinical Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Kim, Young-Seung; Zhou, Yang; Bryant Jr, Henry et al. (2015) Synthesis and characterization of gadolinium-Peptidomimetic complex as an ?v?3 integrin targeted MR contrast agent. Bioorg Med Chem Lett 25:2056-9
Zhou, Yang; Kim, Young-Seung; Milenic, Diane E et al. (2014) In vitro and in vivo analysis of indocyanine green-labeled panitumumab for optical imaging-a cautionary tale. Bioconjug Chem 25:1801-10
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Bumb, Ambika; Sarkar, Susanta K; Billington, Neil et al. (2013) Silica encapsulation of fluorescent nanodiamonds for colloidal stability and facile surface functionalization. J Am Chem Soc 135:7815-8
Kim, Young-Seung; Nwe, Kido; Milenic, Diane E et al. (2012) Synthesis and characterization of ?v??-targeting peptidomimetic chelate conjugates for PET and SPECT imaging. Bioorg Med Chem Lett 22:5517-22
Nwe, Kido; Milenic, Diane E; Ray, Geoffrey L et al. (2012) Preparation of cystamine core dendrimer and antibody-dendrimer conjugates for MRI angiography. Mol Pharm 9:374-81
Nwe, Kido; Kim, Young-Seung; Milenic, Diane E et al. (2012) (111)In- and (203)Pb-Labeled Cyclic RGD Peptide Conjugate as an ?(v)?(3) Integrin-Binding Radiotracer. J Labelled Comp Radiopharm 55:423-426
Huang, Ching-Hui; Nwe, Kido; Al Zaki, Ajlan et al. (2012) Biodegradable polydisulfide dendrimer nanoclusters as MRI contrast agents. ACS Nano 6:9416-24
Bumb, Ambika; Regino, Celeste A S; Egen, Jackson G et al. (2011) Trafficking of a dual-modality magnetic resonance and fluorescence imaging superparamagnetic iron oxide-based nanoprobe to lymph nodes. Mol Imaging Biol 13:1163-72

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