New initiative to detect cancers in earliest stages inside cells

A team of cancer imaging experts at Johns Hopkins has embarked on a five-year research initiative to speed development of early diagnostic tests and new treatments for breast, prostate and other common cancers.

Using advanced imaging tools developed or used for the last decade at Johns Hopkins In-Vivo Cellular and Molecular Imaging Center (ICMIC), the team will search for innovative ways to detect cancers in their earliest stages inside cells, and for ways to stop or kill any of these cancer cells before the disease can spread to other tissues and organs.

"Our next round of studies are aimed at turning what we've shown to be feasible into clinical reality," says cancer imaging researcher Zaver Bhujwalla, Ph.D., who will act as the principal investigator of the expanded initiative. The expansion is made possible with more than $8 million in new grants from the U.S. National Cancer Institute, a member of the National Institutes of Health. "By harnessing the very latest technology in noninvasive imaging — using any single or combination imaging modality of MRI, CT, SPECT, PET, laser optics or ultrasound — we expect to develop tests that detect cancer faster and earlier, distinguish spreading or metastatic tumors from dormant ones, and develop better and more tolerable chemotherapy drugs that only attack cancerous cells, leaving healthy cells alone," she adds.

Bhujwalla says major advances in the last decade in genetic screening, blood testing and tumor biopsy have led to millions more people surviving cancer as a result of early diagnosis and careful treatment, especially chemotherapy and surgery to remove any cancerous tissue. But researchers say the next generation of cancer treatments will target the disease at the earliest, cellular level.

As director of the Johns Hopkins ICMIC, one of 10 such federally funded research centers in the United States, Bhujwalla will oversee more than 30 Johns Hopkins researchers, biostatisticians and lab technicians involved in the effort, advancing several existing and promising discoveries, as well as initiating new ones. Associate directors of the center will be Marty Pomper, M.D., Ph.D.; and Richard Wahl, M.D.

As a professor at the Johns Hopkins University School of Medicine Russell H. Morgan Department of Radiology and the School's Kimmel Cancer Center, she also will serve as principal investigator in all ICMIC studies performed at Johns Hopkins.

For the new round of ICMIC experiments, Bhujwalla has teamed up with Pomper to evaluate image-guided therapy for prostate cancer, a process known as theranostic imaging, which combines diagnostic tools and therapy. Using a triple combination of SPECT and magnetic resonance scanning, along with optical or laser-guided imaging, the Hopkins team will attempt to identify cancerous prostate cells by homing in on a protein found solely on such cells' outside layer. Once these so-called prostate-specific membrane antigens, or PSMAs, are found, researchers intend to use a chemically labeled drug, which can be tracked as it is absorbed into tumors, to kill the cancerous PSMA-labeled prostate cells, leaving healthy cells alone.

In another project, Richard Ambinder, M.D., Ph.D., is also using theranostic imaging in a study of 24 patients with Kaposi's sarcoma, using PET scans, another type of noninvasive imaging, to guide a viral-activated drug, called bortezomib, to kill tumor cells.

Peter van Zijl, Ph.D., and Dmitri Artemov, Ph.D., will study magnetic resonance imaging techniques to detect the earliest possible metabolic and biological changes in breast cancer. Their goal is to find proteins or other small molecules that could serve as early warning signs of cancerous spread and, in combination with other genetic tests, identify women most at risk for cancer spread.

Kristine Glunde, Ph.D., and Xingde Li, Ph.D., are experimenting with laser imaging to analyze collagen fibers in breast cancer tumors. Studies have shown these fibers in distinct patterns in metastatic cancer, patterns that could be useful, in combination with other tests, to distinguish between women who need lymph node biopsy to see if their cancer is spreading, and those who do not.

Also funded by the latest grant will be a group of imaging pilot studies to measure the speed of skin cancer progression, led by Steven An, Ph.D.; to determine the amount of tumor shrinkage during pancreatic cancer treatment, led by Anirban Maitra, M.D., Ph.D.; to learn how cancer spreads to the lungs, led by Phuoc Tran, M.D., Ph.D.; and to evaluate novel treatments to prevent the spread of kidney cancer to the bones, led by Kristy Weber, M.D.

A portion of the grant will also be awarded to Mary-France Penet, Ph.D., for career development, under the direction of Peter Barker, Ph.D. Research infrastructure support in molecular oncology research methods will be co-directed by Venu Raman, Ph.D., and Elizabeth Jaffee, M.D.; in imaging and probe development, directed by Wahl and Artemov; and in biostatistics analysis, directed by Peng Huang, Ph.D.