Title |
Fullerene Immunoconjugates for Cancer Imaging and Treatment
|
Institution |
TDA RESEARCH, INC., WHEAT RIDGE, CO
|
Principal Investigator |
BOLSKAR, ROBERT
|
NCI Program Director |
Anne Menkens
|
Cancer Activity |
Diagnostic Imaging
|
Division |
DCTD
|
Funded Amount |
$200,937
|
Project Dates |
09/26/2007 - 08/31/2009
|
Fiscal Year |
2007
|
Project Type |
Grant
|
Research Topics w/ Percent Relevance |
Cancer Types w/ Percent Relevance |
Chemotherapy (50.0%)
Diagnostic Radiology (100.0%)
Nuclear Magnetic Resonance Imaging (NMR) (100.0%)
Orphan Drug Research (100.0%)
Taxol (50.0%)
|
Melanoma (100.0%)
|
Research Type |
Technology Development and/or Marker Discovery
Systemic Therapies - Discovery and Development
|
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. |