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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43CA128277-01
Application #
7272908
Study Section
Special Emphasis Panel (ZRG1-ONC-T (10))
Program Officer
Menkens, Anne E
Project Start
2007-09-26
Project End
2009-08-31
Budget Start
2007-09-26
Budget End
2008-08-31
Support Year
1
Fiscal Year
2007
Total Cost
$200,937
Indirect Cost
Name
Tda Research, Inc.
Department
Type
DUNS #
181947730
City
Wheat Ridge
State
CO
Country
United States
Zip Code
80033
Ananta, Jeyarama S; Godin, Biana; Sethi, Richa et al. (2010) Geometrical confinement of gadolinium-based contrast agents in nanoporous particles enhances T1 contrast. Nat Nanotechnol 5:815-21