Devkumar Mustafi PhD, Presenter: Pending patent, A Magnetic Resonance Imaging Method using Vanadyl-based Molecular Imaging Probes

Walter J. Liszewski BS, Abstract Co-Author: Nothing to Disclose

Reba Mustafi PhD, Abstract Co-Author: Nothing to Disclose

Anusara Chumsangsri MS, Abstract Co-Author: Nothing to Disclose

Marc Bissonnette MD, Abstract Co-Author: Nothing to Disclose

Gregory Stanislaus Karczmar PhD, Abstract Co-Author: Research Consultant, Perceptive Informatics, Inc Employer Patent Holder, UCHI Patent # 092234-9059-00 titled "A Magnetic Resonance Imaging Method using Vanadyl-based Molecular Imaging Probes" Employer Patent Holder, UCHI Patent titled "High spectral and spatial resolution magnetic resonacne imaging"

Elizabeth Peng BS, Abstract Co-Author: Nothing to Disclose

John W. Ejnik PhD, Abstract Co-Author: Nothing to Disclose

Heather Martin BS, Abstract Co-Author: Nothing to Disclose

et al, Abstract Co-Author: Nothing to Disclose

et al, Abstract Co-Author: Nothing to Disclose

We have developed a novel class of contrast agents that contain VO2+-chelated organic ligands for MRI. The main objectives were to demonstrate that these contrast agents are taken up by highly glycolytically active colon cancer cells and specifically target intracellular protein kinases. Such VO2+-chelates (VCs) could thereby provide high-resolution functional MR images of tumors that cannot be achieved by conventional, non-specific contrast agents.

For these experiments we chose HCA-7 and Caco-2 cells derived from human colonic adenocarcinomas. To demonstrate the uptake of VCs in cancer cells, we carried out in vitro MRI at 4.7 Tesla and atomic absorption (AA) studies with intracellular extracts. The cytosolic fraction of cell extracts was collected for MRI and AA studies. To assess if VCs activate intracellular protein kinases, we measured activations of p-AKT and p-ERK by Western blotting. In addition, MR images of rodent tumors were acquired before and after I.V. injection of contrast media.

Results of MRI and AA studies of soluble extracts after cell treatment with vehicle or VCs showed significant vanadyl concentrations in the cytosolic fraction of cell extracts. These results clearly demonstrate there is intracellular uptake of vanadyl into colon cancer cells exposed to VCs. VCs significantly increased the activation of p-AKT and p-ERK in both HCA-7 and Caco-2 colon cancer cells. Moreover, MRI of rodent tumors demonstrated preferential and persistent uptake of VO2+-chelates in tumors.

Results from in vitro MRI and AA studies provided direct experimental evidence that VCs accumulate within colon cancer cells. Cell signaling experiments indicated that VCs activated key intracellular protein kinases involved in glycolysis. MRI studies in vivo demonstrated preferential accumulation of VCs in rodent tumors.

This is a novel approach to cancer detection with the potential to produce easily tolerated MRI contrast agents that are sensitive to cancer cell metabolism. [Supported by ACS-Illinois grant #06-18].

Mustafi, D, Liszewski, W, Mustafi, R, Chumsangsri, A, Bissonnette, M, Karczmar, G, Peng, E, Ejnik, J, Martin, H, et al, , et al, , A Novel Class of Vanadium-based Magnetic Resonance Imaging Contrast Agents for Targeting Colon Cancer Cells with High Glycolytic Activity.  Radiological Society of North America 2007 Scientific Assembly and Annual Meeting, November 25 - November 30, 2007 ,Chicago IL. http://archive.rsna.org/2007/5006115.html