The findings of a Wayne State University School of Medicine researcher related to finding doses of an anti-angiogenic drug that could enhance treatment of kidney cancer have been published as a feature article in an international journal for cancer research.

Gilda Hillman, Ph.D., associate professor in the Department of Radiation Oncology for the School of Medicine and the Karmanos Cancer Institute, served as principal investigator for "Dynamic Contrast Enhanced Magnetic Resonance Imaging of Vascular Changes Induced by Sunitinib in Papillary Renal Cell Carcinoma Xenograft Tumors." The article was published as the cover story in the September 2009 issue of the journal Neoplasia.

The goal of the study, Dr. Hillman said, was to investigate the effect on tumor vasculature of lower and potentially less toxic doses of Sunitinib, a drug used in the treatment of renal cancer that acts to stop tumors from making new blood vessels. Tumor angiogenesis involves a proliferation of abnormal vessels that are enlarged, disorganized and leaky. The condition impairs blood and oxygen supply to tumors, which, in turn, compromises the delivery and efficacy of chemotherapy drugs and radiotherapy.

While Sunitinib has proved effective and has helped prolong patients’ lives, long-term control of renal carcinoma has not been achieved. Dr. Hillman wanted to determine what doses of the drug could induce regularization of tumor vessels by reducing the growth of inefficient blood vessels and thereby improving blood flow. Dr. Hillman had previously established a pre-clinical model of metastatic renal cell carcinoma in her laboratory and used it to treat kidney tumors with various doses of Sunitinib. Dr. Hillman’s team then studied the vascular changes in murine kidney tumors associated with each dose. The team used dynamic contrast-enhanced MRI imaging, a technology that can be used in humans.

The study assessed the effect of Sunitinib on both the right cancerous kidney and the left normal kidney in mice. The team then compared the data obtained from DCE-MRI imaging of tumors to the data produced by histological staining of tumor sections and determined a dose of Sunitinib that caused regularization of blood flow and thinning of vessels while producing milder effects on blood vessels in the normal kidney.

“These studies have established the feasibility of using DCE-MRI in animal models to assess early vascular changes in tumors induced by anti-angiogenic therapy that could be helpful for scheduling chemotherapy or radiotherapy and increase the efficacy of anti-angiogenic therapy,” said Dr. Hillman, who works with department Chair Andre Konski, M.D., M.B.A., in designing clinical trials of radiotherapy and anti-angiogenic drugs. “This approach using DCE-MRI imaging can be applied to treatment of human cancer.”

The research team included Vinita Singh-Gupta, Ph.D.; Hao Zhang, M.D.; Christopher Yunker and Amit Patel, who was instrumental in data organization and presentation. Mark Haacke, Ph.D., director of the MR Research Facility and a professor of Radiology, collaborated on the study for consulting on imaging parameters conditions and interpretation of MRI data and analysis. He was assisted by Yimin Shen, Ph.D., and several students involved in data analysis. Dr. Haacke’s Ph.D. student, Areen Al Bashir, is participating in imaging data analysis and is using this research as the major topic of her thesis.

Pfizer funded the two-year study with a $264,468 grant.