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Abstract
Grant Number: 1R43CA128277-01 Project Title: Fullerene Immunoconjugates for Cancer Imaging and Treatment
PI Information: Name Title BOLSKAR, ROBERT D. bolskar@tda.com SENIOR CHEMIST Abstract: DESCRIPTION (provided by applicant): In this collaborative project between TDA Research, Rice University and M.D. Anderson Cancer Center, we will develop new metallofullerene-taxol-antibody conjugates for combined cancer imaging and treatment. Fullerenes are non-toxic carbon cage molecules with a rich derivatization chemistry useful for conjugating drug molecules, to generate therapeutic prodrugs. The endohedral metallofullerene Gd@C60 have been shown in prior studies to function effectively as T1 imaging agents, including for cellular labeling. Gd@C60 offers a safe contrast agent platform lacking the potential for free Gd3+ toxicity due to the very high stability of endohedral Gd sequestration, which is not compromised under physiological conditions. We will chemically conjugate paclitaxel groups to a Gd@C60 derivative to form a new combined therapeutic/imaging agent prodrug. Using the Gd@C60-paclitaxel conjugates, new immunoconjugates with the anti-gp240 melanoma antibody ZME-018 will be formed and tested for cellular uptake, for MRI contrast agent efficacy and for cytotoxicity against melanoma cancer cells in vitro. The strategy of combining antibody targeting with a therapeutic MR imaging agent will improve melanoma diagnosis, treatment and patient outcome, and has the potential for targeting multiple drugs to cancerous cells at the same time.
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Institution: TDA RESEARCH, INC. 12345 W 52ND AVE WHEAT RIDGE, CO 800331916 Fiscal Year: 2007 Department: Project Start: 26-SEP-2007 Project End: 31-AUG-2009 ICD: NATIONAL CANCER INSTITUTE IRG: ZRG1