Devkumar Mustafi PhD, Presenter: Nothing to Disclose

Jesse Ward PhD, Abstract Co-Author: Nothing to Disclose

Urszula Dougherty MS, Abstract Co-Author: Nothing to Disclose

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

Stefan Vogt PhD, Abstract Co-Author: Nothing to Disclose

Gregory Stanislaus Karczmar PhD, Abstract Co-Author: Research Consultant, Perceptive Informatics, Inc Research Consultant, BioClinica, Inc

Colon cancer is one of the most common forms of cancer and its early detection can vastly improve outcomes. MRI contrast agents can greatly improve diagnostic accuracy. Here we compare a new MRI contrast agent that is sensitive to glycolysis to a conventional Gd-based agent. Specifically, we report on: (1) MRI using Gd and a cancer specific, vanadium-based agent (VC) to measure contrast improvement in vivo, and (2) X-ray fluorescence microscopy (XFM) to quantify contrast uptake directly and to determine cellular and sub-cellular distributions in situ.

Colonic tumors were induced in CF1 female mice (n=25) with i.p. injection of azoxymethane weekly for 2 weeks (10 mg/kg), followed by 2 cycles of 2.5% dextran sulfate sodium in the drinking water for 5 days. This model mimics many clinical and pathological features of colitis-associated colon cancer. T1/T2*-weighted and contrast-enhanced MR images were acquired using a 9.4T Bruker scanner. The day after the last in vivo MRI, mice were sacrificed after Gd and/or VC injection I.V. (0.13 mmol/kg), colons (normal and tumors) were harvested and ~5 μm slices were sectioned for XFM and H&E. XFM images were acquired using an X-ray microprobe at the Argonne Natl Lab. Concentrations of metal ions and other elements were determined based on the tissue thickness on the XFM slide.

Values of T2 distinguished normal colon from colonic wall focally thickened with tumor (p<0.005). From DCEMRI, the values of Ktrans (min-1) were found to be 0.12±0.01 for normal colon and 0.61±0.05 for tumors (p<0.001). For VC uptake in implanted rodent tumors, peak enhancements in tumor and muscle of 0.225 ± 0.052 and 0.05 ± 0.018, respectively, were measured during the injection phase - a nearly 5-fold increase in enhancement between tumor and muscle with p < 0.001. XFM studies of normal and colon cancer-bearing mice suggest specific uptake of VC in tumor regions, while Gd distributes uniformly. High-resolution (0.3 micron) scans of tumors revealed that the uptake of VC in cancer cells is ~8-fold higher compared to the background VC signal.

VC-based agents preferentially accumulate in cancer cells, offering an advantage over less selective Gd-based agents.

VCs accumulate selectively in tumors - improve cancer diagnosis and staging. MRI and XFM studies of early colon cancer in mice may improve new information regarding cancer progression and therapies.

Mustafi, D, Ward, J, Dougherty, U, Bissonnette, M, Vogt, S, Karczmar, G, Evaluation of Vanadium-based Contrast Agents for Detection of Early Murine Colon Cancer Using Magnetic Resonance Imaging and X-ray Fluorescence Microscopy.  Radiological Society of North America 2012 Scientific Assembly and Annual Meeting, November 25 - November 30, 2012 ,Chicago IL. http://archive.rsna.org/2012/12043498.html