January 22, 2010

Study of colorectal cancer imaging techniques bolstered

Study of colorectal cancer imaging techniques bolstered

Vanderbilt's H. Charles Manning, Ph.D., has received two stimulus grants from the National Cancer Institute to study imaging techniques in colorectal cancer.

The grants, totaling more than $1.6 million over two years, are part of the federal government's stimulus package funded through the American Recovery and Reinvestment Act of 2009.

“We were honored to receive these awards,” said Manning, assistant professor of Radiology and Radiological Sciences, Neurosurgery, Biomedical Engineering, and Chemical and Physical Biology. “I am

H. Charles Manning, Ph.D.

H. Charles Manning, Ph.D.

The first award is a Challenge Grant which focuses on the broad area of biomarker discovery.

Manning and his colleagues will be investigating a tracer called 18F-fluorothymidine (FLT) used in positron emission tomography (PET) scans.

FLT is injected into a patient with cancer and may localize in tumors, showing up as a bright spot on a PET scan under certain conditions.

“We know FLT measures a specific aspect of cell proliferation, making it potentially useful for cancer imaging,” Manning said. “FLT measures a protein called thymidine kinase 1 (TK1), which is involved in DNA synthesis. What is poorly understood is how cancer cells regulate TK1.

“We also know that cells can synthesize DNA using a different pathway unmeasurable with FLT-PET, so we need to know more about the types of cancers that can be evaluated with FLT and how they are put together in a regulatory fashion.”

Having the capacity to understand and measure cell proliferation and response to treatments may be a critical component of personalized medicine. Right now, physicians may have to wait weeks to find out if a cancer drug is shrinking a tumor in an individual patient. More targeted imaging could speed up the process.

“The promise of molecular imaging is to rapidly and noninvasively interrogate tissues of interest without tissue sampling, such as biopsy,” said Manning.

“Molecular imaging biomarkers, like FLT PET, may enable us to determine whether a drug is working as early as a few hours after administration as well as predict whether patients will continue to respond over time. This information could spare patients the expense and potential side effects of ineffective therapies.”

The ability to predict and determine molecular activity in cancer cells could help clinicians choose the therapy most likely to help individual patients.

The imaging study will be conducted in conjunction with ongoing therapeutic clinical trials with colorectal cancer patients at Vanderbilt-Ingram Cancer Center.

“Going forward, we hope to understand more about the underlying genes and proteins that affect FLT-PET,” Manning explained.

The second grant is a five-year RO1 award, with the first two years supported by stimulus funds.

That project will combine and compare three unique imaging modalities, including FLT-PET, Annexin-V SPECT imaging, and apparent diffusion coefficient mapping via MRI (ADC-MRI). The study will be performed in mouse models of colorectal cancer with the goal of understanding how synthesis of imaging metrics, or multimodality imaging, can be used to better understand cell proliferation and cell death in tumors.

The research by Manning and his colleagues is an outgrowth of the Gastrointestinal Specialized Program of Research Excellence (SPORE) program at VICC. The GI SPORE is led by Robert Coffey Jr., M.D., Ingram Professor of Cancer Research.