Scientific Overview: Noninvasive Imaging and Radiation Biology

Research Interests

In July 2005, the Laboratory of Noninvasive Imaging and Radiation Biology originated as an outgrowth and expansion of activities of the Laboratory of Molecular Oncology. This lab is devoted to both noninvasive imaging (i.e., the generation and analysis of images or depictions of structure and selected functions in living organisms without surgically or mechanically penetrating a body cavity) and radiation biology (which involves analysis of the consequences of external and internal radiation exposure in living organisms).

The lab’s work follows three common themes:

• Development and use of laboratory models that address medical imaging and radiation exposure problems.
• Advancement of technology in imaging and radiation biology, including novel agents, probes, and reporters; new strategies for tackling research problems; and new instrumentation.
• Pursuit of two-way translation between the laboratory and the clinical setting, i.e., using examples of human disease to design and improve laboratory model systems for study, as well as moving new discoveries from the laboratory benchtop to the patient’s bedside.

We depend heavily upon access to sophisticated instruments and equipment, including nuclear imaging cameras; planar and tomographic X-ray units; clinical and research ultrasonography units; fluorescence detection systems; and cell and organism irradiation capability. Because of the equipment- and expertise-intensive nature of our projects, we could not succeed without the help of our valued collaborators. During this past year we have acquired two new state-of-the-art noninvasive imaging instruments: a Vevo 770 high-resolution micro-ultrasound imaging system (VisualSonics) and a nanoSPECT/CT imaging unit (BioScan), and we have continued to pursue research projects in radiation biology, nuclear medicine, and multimodality imaging.

One established research project continues work begun by Nigel Crompton at the Paul Scherrer Institute in Switzerland, now performed in collaboration with the radiation oncology service at Saint Mary’s Health Care. This project seeks to predict the sensitivity of a patient’s normal tissues to irradiation that is being administered for treatment of a serious condition such as cancer. For this project a sample of the patient’s blood is drawn before radiation therapy. The blood sample is then irradiated (outside the patient) under precise conditions of exposure, treated with fluorescent molecules that detect certain types of blood cells (lymphocytes), and then analyzed by fluorescence-activated cell sorting (FACS) for evidence of lymphocyte death. In Switzerland, Dr. Crompton established a close correlation between lymphocyte death and a patient’s normal tissue tolerance to irradiation. We are now determining whether western Michigan patients respond similarly, as well as investigating the effects of patient age, gender, and administered radiation dose on the apoptotic response.

A new radiation biology project this year, in collaboration with Weiwen Deng and Aly Mageed of DeVos Children’s Hospital, investigates a new approach for treating graft-versus-host disease in mice undergoing bone marrow transplantation, with planned extension to human patients in the near future.

Our major established project in nuclear medicine continues work initiated by Dr. Hay and colleagues while he was a member of the Laboratory of Molecular Oncology. Since 2001 we have been evaluating radioactive antibodies and smaller molecules that attach to the Met receptor tyrosine kinase, collectively designated Met-avid radiopharmaceuticals (MARPs). Met plays a key role in causing cancers to become more aggressive, so that they spread to nearby tissues (invasion) and/or travel through the bloodstream or lymph channels to distant organs (metastasis). We previously showed that both large and small MARPs are useful for nuclear imaging of Met-expressing human tumors (xenografts) grown under the skin of immunodeficient mice. During the past year, in collaboration with our colleagues at VARI and with our outside collaborators at DVAHS, ApoLife, and MSU, we have been evaluating new ways of complexing radioactive atoms with MARPs for improved ease of use and future clinical applications.

In 2006 we began a multimodality noninvasive imaging program for evaluating the growth, Met expression, and response to therapy of aggressive human tumor xenografts grown orthotopically in immunodeficient mice. Employing a combination of high-resolution ultrasound with and without contrast agents, planar and tomographic nuclear imaging, and CT imaging, we are now acquiring data for tumors of the brain, pancreas, adrenals, and bone.

External Collaborators

Our lab depends critically on intramural and extramural collaborations to address our research themes. Our extramural collaborators include scientists and physicians at the Department of Veterans Affairs Healthcare System in Ann Arbor; the University of Michigan in Ann Arbor; Michigan State University in East Lansing; ApoLife, Inc., in Detroit; Henry Ford Hospital in Detroit; West Michigan Heart, P.C., in Grand Rapids; DeVos Children’s Hospital in Grand Rapids; St. Mary’s Health Care in Grand Rapids; Fred Hutchinson Cancer Research Center in Seattle; the Gerald P. Murphy Foundation in West Lafayette, Indiana; the National Cancer Institute in Bethesda, Maryland; the University of Illinois in Champaign-Urbana; and VisualSonics, Inc., in Toronto.