Advancing Discovery and Its Application

Cancer Imaging and Molecular Sensing

The Opportunity

Over the last quarter century, investment in cancer imaging has dramatically improved the quality of patient care by making it possible to detect tumors much earlier when they are easier to treat and by permitting more precise therapy or surgery. New imaging techniques can be used to determine, in real time, if a tumor has invaded vital tissue, grown around blood vessels, or spread to distant organs. Imaging supports various tumor-destroying approaches (chemicals, radiation, gene therapy, heat, and cold) to minimize surgical trauma and damage to healthy tissue, shorten recovery time, and reduce healthcare costs. Molecular or "functional" imaging of the physiological, cellular, or molecular processes in living tissue can sometimes allow physicians to monitor their patients' progress and response to therapy without the need for biopsies.

Indeed, more imaging resources are devoted to the study and treatment of cancer than to any other disease and, in many ways, the needs of cancer research and treatment drive the direction of imaging research. As we learn more about the molecular basis for cancer, this level of sustained investment in cancer imaging becomes even more necessary and productive. For example:

• Micro-imaging technologies are needed to fully utilize the increasing number of mouse models of human cancer to uncover the genetic basis of specific tumors.
• Functional imaging needs to be developed to study how newly discovered defects in genes and proteins interact to cause cancer.

Recent discoveries in cancer signature and molecular therapeutic research demand new ways to assess the effectiveness of molecularly targeted treatments in clinical trial settings.

At the same time, we must invest in applying the new technologies emerging from the study of nanoscience that promise to give biomedical researchers and healthcare providers even more options for detecting and monitoring biologic events in cancer. Researchers are designing molecular biosensors to be injected into the bloodstream to seek out and destroy cancer cells. These biosensors, about 10,000 times smaller than the head of a pin, will also allow physicians to image the cancer and follow the patient's response to therapy - all with minimal side effects and little disruption of healthy tissue.

NCI has a unique opportunity to further improve cancer imaging and molecular sensing technologies to ensure earlier and more accurate diagnoses for cancer patients, reduce the number of invasive interventions, guide individualized therapies, and improve monitoring of patient response to treatment. With additional investment in research and development, significant advances in these areas will increasingly save and improve lives.

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Progress in Pursuit of Our Goal

NCI's investment in developing better imaging technologies for both cancer research and clinical practice are tangibly impacting patient's lives.

Developing Better Imaging Technologies and Techniques

NCI has played a major role in fostering functional imaging through initiatives such as In Vivo Cellular and Molecular Imaging Centers (ICMICs). With five Centers established as of 2002, each ICMIC brings together experts from diverse scientific and technological backgrounds to conduct multidisciplinary research on cellular and molecular imaging in cancer. NCI is providing support for 14 potential ICMIC sites, including a site for researching functional imaging of low activity genes.

NCI's Development of Clinical Imaging Drugs and Enhancers (DCIDE) program is continuing to foster the development of new imaging contrast agents and molecular probes to improve the diagnosis and treatment of cancer. By its second year, DCIDE will be developing as many as seven imaging agents or probes designed to measure blood vessel formation and cell death, evaluate cell growth, and enhance visualization of prostate and other cancers.

Several of NCI's Progress Review Groups have stressed the need for publicly available imaging databases to support optimal growth in imaging research and technology. The NCI-supported Molecular Imaging Database (MOLI), expected to be released in July 2002, will help researchers develop new imaging agents and help clinicians find existing agents for imaging specific cancers. By early 2003, NCI's Lung Imaging Database Consortium will provide databanks of standardized digital image data from cancer patients, together with clinical outcome information, a resource much requested by researchers.

Researchers of the Mouse Models of Human Cancer Consortium (MMHCC) are developing inventive imaging modalities for use in pre-clinical studies. One group is using MRI to learn how to deliver anti-tumor therapy to the brain using neural stem cells. Other researchers use a unique micro-computed tomography imaging (micro-CT) contrast agent to visualize metastatic tumors in the livers of mice with invasive colon cancer. This team developed a second agent to track metastases in other organs throughout the mouse.

Bringing Advances in Imaging to Cancer Care

NCI is supporting clinical trial research to move promising imaging advances from discovery and development to clinical use. New cancer imaging technologies and techniques are often evaluated through one of NCI's clinical trials cooperative groups. These groups are networks of healthcare professionals affiliated with medical schools, teaching hospitals, and community-based cancer treatment centers. For example, the American College of Radiology Imaging Network (ACRIN) recently completed a study to determine whether computed tomography (CT) scanning - a technique sometimes known as "virtual colonoscopy" - is sufficiently reliable for colon cancer screening to warrant further study. Based on their promising results, a large-scale trial will follow this study.

Other ACRIN efforts are underway to determine:

• Whether combined Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopic Imaging can be used to accurately localize and diagnose prostate cancer.
• Whether CT scanning can be used to reliably measure tumor volume of supraglottic cancer.
• How the drug Gleevec™ impacts the biology of Gastrointestinal Stromal Tumors (GIST).
• Whether CT or MRI can improve the pre-treatment evaluation of invasive cervical cancer.

The Digital Mammography Imaging Screening Trial, another large-scale ACRIN trial, is comparing the diagnostic power of digital mammography to conventional, film-based mammography. Over 6,000 women have enrolled at 18 locations across the United States, and another 10 sites will be added in 2002. ACRIN is also helping to design and conduct the NCI-funded National Lung Screening Trial (NLST), which will determine the merit of spiral computed tomography (CT) for lung cancer detection compared to X-ray screening. NLST will utilize the infrastructure developed in the up-and-running Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to enroll 50,000 current or former smokers for screening at 30 study sites throughout the United States.

Other NCI-sponsored networks are also evaluating the use of imaging technologies. For example, the American College of Surgeons Oncology Group is determining the value of positron emission tomography, or PET, for lung cancer staging. In addition to supporting these and other large-scale clinical trials for imaging technologies, NCI is providing infrastructure to support early phase clinical testing of imaging agents and probes at various centers and NCI-supported programs around the country.

NCI also recognizes the crucial place of partnerships to translate budding imaging technologies into practices that improve patient care. For example, NCI's Novel Imaging Technologies program supports collaboration of academic scientists with industry and foreign institutes to create unique imaging technology. One team of NCI-funded investigators is developing the next generation of the PET/CT scanner for improved localization and evaluation of difficult-to-pinpoint cancers and therapeutic monitoring.

Furthermore, NCI is working to integrate imaging into a broad cross section of cancer clinical trials as a way to make the trials more efficient. For example, NCI cooperative groups are working with the Cancer Therapy Evaluation Program, or CTEP, to identify how to use imaging as a biomarker or surrogate marker - perhaps instead of a biopsy- to demonstrate the effectiveness of a treatment. In April 2002, NCI held a workshop, "Role of Biological Imaging in Radiation Oncology." Scientists identified the next steps needed to integrate functional and molecular imaging with radiation therapy to improve tumor control while minimizing damage to healthy tissues.

The Plan - Cancer Imaging and Molecular Sensing

Stimulate and accelerate discovery and development of imaging methods and biosensors to identify the biological and molecular properties of precancerous or cancerous cells that will predict clinical course and response to interventions. Advance the development and implementation of minimally invasive image-guided therapies.

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Functional Imaging of Low Activity Genes by ICMIC Researchers

For years, cancer researchers have been studying certain highly important, but low activity, genes in their work with animal models. The "activity" of a gene - usually measured by how much protein it is making - helps the scientist understand how the gene is affecting the biology of the cell. However, the protein levels of low activity genes are often too minute to measure. To overcome this difficulty, one team of In Vivo Cellular and Molecular Imaging Center (ICMIC) researchers, studying the gene for prostate specific antigen (PSA) in mice, recently developed a technique known as two-step transcriptional amplification (TSTA).

In the first step, they changed the mouse's PSA gene so that it would produce a small amount of a special protein whenever the PSA gene was active. For the second step they added a separate gene that will produce large quantities of an easily measured fluorescent chemical, when in the presence of even small amounts of the special protein. Then, by measuring fluorescence, they know the activity level of the PSA gene. The ICMIC researchers expect to develop the TSTA approach for study of a variety of low activity genes, adding to our understanding of a number of cancers and how to prevent, detect, and treat them.

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Nanoscience - New Opportunities for Detection, Monitoring, and Intervention

Recent advances in understanding the molecular basis of cancer raise the possibility of diagnosing, treating, and monitoring cancer with increasingly specific, even individualized therapies. A number of researchers in the field of nanoscience have started to develop synthetic spheres of molecules that can seek out and examine cancer cells. These special spheres, referred to as nanoparticles, because they are thousands of times smaller than a single cell, can carry a variety of specially designed molecular-sized attachments that allow them to act as a type of biosensor. These remarkable nanotechnology innovations can be designed to seek out, analyze, and treat cancer cells - all without harming healthy cells.

NCI-supported researchers are developing such a biosensor to locate brain tumor cells and tag them for easy imaging. The biosensor can then be targeted with an external laser beam to activate a special chemical attachment designed to kill the cell. Other exciting projects in nanotechnology are taking shape in laboratories across the country. Although human testing is years away, with proper funding and interdisciplinary cooperation, scientists envision making significant progress in this field within 5 to 10 years. Ultimately we look for a day when many cancer patients will be effectively diagnosed, treated, and monitored with a simple injection and non-invasive monitoring rather than with surgery, chemotherapy, radiation, or other conventional therapies.

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Molecular imaging techniques do not actually reveal molecules themselves, but they detect signals that indicate the presence of biochemical activity and changes, such as cell growth or death. Thus, molecular imaging is often described as "functional," because the processes being imaged are active and constantly changing. Back.

Nanoscience is the study of objects and phenomena on extremely small scales. Back.