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Scientific Priorities for Cancer Research: NCI's Extraordinary Opportunities |
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Cancer Imaging
Goal
The Opportunity
Progress in Pursuit of Our Goal
Highlights of Recent Advances in Cancer Imaging
2003 Plan and Budget Increase Request
Goal
Accelerate discovery and development of imaging methods that will predict clinical course and response to interventions.
The Opportunity
As recently as 25 years ago, a physician or surgeon who suspected the presence of a tumor in a patient had few options. The normal course of events would be to order x-ray studies to find the tumor's exact location, schedule the patient for surgery, excise a portion of the unhealthy tissue for biopsy, remove the tumor, and explore surrounding tissues to determine if the cancer had spread.
But over the last quarter century, improvements in imaging technology have substantially broadened the range of medical options. Physicians can:
- Use the power of imaging technology now available to get much clearer and more detailed pictures of organs and tissues.
- View far more than anatomical structures such as bones, organs, and tumors.
- Use "functional imaging" for the visualization of physiological, cellular, or molecular processes in living tissue to examine activities such as blood flow, oxygen consumption, or glucose metabolism as they take place.
Modern imaging technology already has had lifesaving effects on our ability to detect cancer early and more accurately diagnose the disease.
- X-ray mammography, for example, has revealed the presence of very small cancers in thousands of women before the tumors could be detected by physical examination.
- Computed tomography (CT) can show if a tumor has invaded vital tissue, grown around blood vessels, or spread to distant organs. As the science continues to advance, we will be able to detect changes in the workings of a cell as it becomes malignant and use this information to diagnose cancer earlier.
Eventually, we may be able to detect changes in the activity and function of specific genes in a patient's cancer cells, and use that information to choose the best treatment option.
- In addition to using CT and other imaging technologies to guide treatment choices, scientists have developed methods for combining imaging techniques with radiation sources and high-performance computing. This serves to better target radiation treatments to a tumor's three-dimensional contours, thus minimizing damage to surrounding, healthy tissue.
- Moreover, with today's technology, we can also identify the molecular characteristics of a tumor and use that information to predict how it will respond to certain treatments. With a visual image of how glucose is being used in cancer cells, we can tell - without the need for a biopsy - how a tumor is responding to a recently administered treatment.
- Oncologists also increasingly rely on image-guided therapy, in which imaging is combined with various tumor-killing approaches (toxic chemicals, gene therapy, heat, and cold). By allowing physicians to better distinguish between cancerous and normal tissue and target treatments to diseased tissues, image-guided therapy can:
- Minimize surgical trauma
- Shorten recovery time
- Improve patient quality of life
- Reduce health care costs
NCI's opportunity is to further improve cancer imaging technologies with goals of:
- Ensuring earlier and more accurate diagnoses for more cancer patients.
- Reducing the number of invasive therapies needed to treat their illnesses.
- Improving physicians' abilities to monitor patients' responses to treatment.
With investments in research and development, significant advances in cancer imaging are now possible and will ultimately save more lives.
Progress in Pursuit of Our Goal
Advances in cancer imaging research and technology over the last 25 years have demonstrated their potential to profoundly affect the practice of oncology and extend patients' lives, and NCI's continued investment is yielding tangible progress in developing better imaging technologies for both cancer research and clinical practice.
Developing Better Imaging Technologies and Techniques
In Vivo Cellular and Molecular Imaging Centers
Development of Clinical Imaging Drugs and Enhancers
Small Animal Imaging Resource Programs
Miniaturized Optical Probes
Bringing Advances in Imaging to Cancer Care
Developing Better Imaging Technologies and Techniques
NCI has played a major role in fostering molecular or functional imaging (Molecular imaging techniques do not actually reveal molecules themselves, but 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.)
Through initiatives such as In Vivo Cellular and Molecular Imaging Centers (ICMICs), NCI has nurtured and promoted molecular imaging by supporting essential infrastructure and providing career stability to investigators in this emerging field of research. Each Center brings together experts such as biomedical engineers, cellular and molecular biologists, pharmacologists, and imaging scientists to conduct a program of multidisciplinary research on cellular and molecular imaging in cancer.
One of the ICMICs has led the way in developing "smart contrast agents." When smart contrast agents are injected into the body, they are undetectable. However, when they come into contact with tumor-associated enzymes called proteases, the smart agents change shape and become fluorescent. The fluorescent signal can then be detected using sophisticated imaging devices.
This first generation of smart agents are being further refined and developed by ICMIC investigators and will have important applications in tumor detection and therapy assessment in the future.
At the start of 2000, NCI established ICMICs at three sites around the country. The Institute has also awarded planning grants to 16 universities and research centers to begin to bring together investigators from a range of fields and initiate research projects in molecular imaging. NCI will select two of these to become full-fledged Centers by the end of 2001.
In addition to their research activities, ICMICs will train new investigators and provide established investigators an opportunity to develop a multidisciplinary understanding of imaging, the basic science of cancer, and cancer care.
NCI is also helping to foster the development of new imaging contrast agents and molecular probes to improve the diagnosis and treatment of cancer through the Development of Clinical Imaging Drugs and Enhancers (DCIDE) program. In the first year of DCIDE, two agents were selected for further development:
- A new contrast agent that enhances positron emission tomography (PET) imaging by targeting elevated levels of an enzyme present in prostate and other cancers
- A probe that can improve the accuracy with which magnetic resonance imaging (MRI) can reveal the earliest stages of the new blood vessel growth that accompanies a developing tumor.
Animal models of cancers play an invaluable role in research, enabling scientists to:
- Investigate the development and progression of cancer.
- Test new approaches to detection, diagnosis, and imaging.
- Evaluate prevention and treatment.
With improved, genetically engineered mouse models for cancer becoming more widely available, investigators are able to use laboratory mice to study the development and spread of cancer and to test improvements in cancer imaging through the use of specialized equipment and techniques for imaging small animals.
Since 1999, NCI has funded Small Animal Imaging Resource Programs at five research centers around the country to:
- Make the necessary equipment and personnel available to investigators.
- Improve and enhance technologies and techniques for imaging small animals.
Investigators working with the Small Animal Imaging Resource Program at one university, for example, have been exploring the use of diffusion MRI, which measures the movement of water through and between cells, for imaging brain tumors. After validating their approach in small animals, imaging specialists have begun to test this new form of MRI in patients with brain tumors and other cancers. Initial results in patients, especially children, look very promising. If proven effective, diffusion MRI could dramatically reduce the time required to determine whether cancer patients are responding to therapy.
Given the success of the Small Animal Imaging Resource Programs to date, NCI funded five additional programs in 2001.
In addition, the Institute is actively working to foster broader use of these technologies. For example, NCI co-sponsored a conference on the techniques of small animal imaging in September 2001, and has awarded supplemental funding to a number of scientists involved in the Mouse Models of Human Cancers Consortium to incorporate imaging research into their work.
NCI, with the National Science Foundation, is cultivating further advances in the development of noninvasive imaging, monitoring, and therapeutic systems, with two projects focusing on the development of miniaturized optical probes. These probes, which provide very high-resolution images, are capable of detecting changes at the molecular level.
Bringing Advances in Imaging to Cancer Care
New cancer imaging technologies and techniques often undergo evaluation through one of NCI's clinical trials cooperative groups. These are networks of health care professionals affiliated with medical schools, teaching hospitals, and community-based cancer treatment centers. For example:
- NCI's newest cooperative group, the American College of Radiology Imaging Network (ACRIN), is assessing the value of computed tomography (CT) scanning in screening patients for colon cancer, a technique sometimes known as "virtual colonoscopy." Because patient cooperation is critical to the success of any type of cancer screening, another group of NCI-funded investigators is also looking at patient preferences as one component of their comparisons of virtual colonoscopy and more traditional methods of colon cancer screening.
ACRIN investigators are also evaluating the use of CT, MRI, and traditional tests for determining the spread of cervical cancer. To definitively answer questions about the value of digital mammography for breast cancer screening, ACRIN investigators have launched the largest study ever to compare conventional and digital mammography. They plan to compare the two methods in nearly 50,000 women over the next few years.
- The American College of Surgeons Oncology Group is actively studying the use of PET scanning in patients with lung and esophageal cancer, to determine how far the disease has advanced.
- Investigators involved in the Lung Cancer Screening Study are comparing the use of spiral CT with traditional chest x-rays in screening for lung cancer.
- A number of other investigators around the country are working to improve diagnostic imaging and image-guided therapy for prostate cancer.
In addition to evaluating the use of various imaging technologies and screening and treatment procedures, NCI-supported scientists also are using sophisticated imaging to assess the effects of new cancer drugs. For example, with many drugs that prevent the growth of new blood vessels, tumor shrinkage may not be readily apparent for some time. In cases such as these, functional imaging techniques can reveal whether the tumor is responding to therapy.
The integration of new imaging technologies in radiation oncology will not only improve the targeting of a tumor but will allow for the delivery of a more exacting radiation dose to areas within the tumor defined by functional imaging. This targeting has the potential to not only to improve tumor control, but also minimize toxicity.
This complex technology requires improved treatment planning, quality assurance, and data transfer. NCI is supporting a consortium to develop the necessary tools through the Advanced Technology Radiation Therapy Clinical Trials program.
Biomedical opportunities and scientific advances drive technology development in cancer imaging, but NCI recognizes that the regulatory environment in which this development takes place is critically important. NCI facilitates the transition of emerging cancer imaging technologies into medical practice through "sounding board" of Federal agency staff that advises investigators and manufacturers seeking to bring new imaging technologies to the marketplace.
This group, the Interagency Council on Biomedical Imaging in Oncology, consists of staff from NCI, the Food and Drug Administration (FDA), and the Centers for Medicare and Medicaid Services (formerly the Health Care Financing Administration). Council members provide advice to technology developers from academia and industry and discuss the evaluation of emerging technologies.
Since September 1999, NCI has also co-sponsored with industry an annual national conference on biomedical imaging in oncology that focuses on the research, regulatory, and reimbursement pathways of technology development.
Highlights of Recent Advances in Cancer Imaging
High-Powered Microscope Tracks Cell Changes
With funding from NCI, a multidisciplinary team of physicists, biologists, optical experts, and chemists has developed a new type of microscope combining the capabilities of nuclear magnetic resonance imaging with those of a traditional microscope. Using the combined microscope, investigators can:
- Examine how living cells react to changes in their environment.
- Track the development of cancer.
- Study how cancer cells respond to treatment.
In light of its potential significance for biomedical research, Discover Magazine recognized the new microscope and the leader of the research team that developed it, with its 2001 Award for Technological Innovation in Health.
New Imaging Tools Provide More Accurate and Complete Diagnosis
Two groups of NCI-supported investigators recently received Food and Drug Administration approval for computer-aided diagnosis systems to help radiologists assess the results of mammograms and chest x-rays. In these systems, computers are programmed to identify and highlight suspicious "hot spots" to ensure that all potentially cancerous points are examined.
Optical Biopsies an Option for the Future
NCI-funded scientists are developing imaging systems that may permit patients to undergo "optical biopsies" in the future and allow physicians to diagnose cancer without the need for tissue samples. By modifying endoscopes and similar instruments to provide very high-resolution images for examining the gastrointestinal system, lungs, and other internal organs, investigators can now identify the cellular changes typical of early cancer when it is most treatable. In cases where these more powerful images can rule out cancer, such optical biopsies will allow patients to avoid unnecessary and painful tissue biopsies.
The Plan - Cancer Imaging
Goal
Accelerate discovery, development, validation, and clinical feasibility of imaging methods to identify the biological and molecular properties of precancerous or cancerous cells that will predict clinical course and response to interventions.
Fiscal Year 2003 Objectives, Milestones, and Funding Increases Needed
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| Objective 1: Expand the discovery, design, and development of novel imaging agents and devices. |
- Establish two additional In Vivo Cellular and Molecular Imaging Centers (ICMICs) to foster multidisciplinary research on cellular and molecular imaging in cancer.
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$4.00 M |
- Establish a Network for Optical Technologies Development.
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$4.00 M |
- Increase the number of imaging agents supported by the Development of Clinical Imaging Drugs and Enhancers Program from 6 to 10 per year.
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$4.00 M |
- Use research supplements to increase collaborations between Small Animal Imaging Resource Programs (SAIRPs) and other NCI programs such as the Mouse Models of Human Cancers Consortium.
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$2.00 M |
- Speed the development of specific imaging agents by funding grantees in a variety of NCI programs, such as ICMICs, SAIRPs, Interdisciplinary Research Teams for Molecular Target Assessment, Molecular Target Drug Discovery, and Molecular Target Laboratories.
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$2.00 M |
- In collaboration with the developers, provide to academic institutions for feasibility testing, innovative imaging device prototypes, selected through a new competitive program, that have a limited market or face other barriers to commercialization.
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$5.00 M |
- Support and add information to a publicly available database of imaging agents for the research community.
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$0.10 M |
- Establish data banks of standardized digital image data (such as virtual colonoscopy, digital mammography, digital chest imaging, and optical imaging for applications such as cervical, prostate, and oral cancers) associated with known clinical outcomes to provide research resources for a variety of investigators.
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$2.00 M |
- Fund six to eight grants to develop and test image processing and analysis algorithms (artificial intelligence) using these standardized data sets.
|
$2.00 M |
| TOTAL |
$25.1 M |
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| Objective 2: Integrate molecular and functional imaging methods into therapeutic clinical trials. |
- Increase the contract support for early clinical trials of imaging agents (safety and efficacy studies) from 8 to 12 trials per year.
|
$2.00 M |
- Provide expertise to clinical trials that use imaging by funding supplements or grants for 10 to 15 imaging cores within NCI-funded Cancer Centers.
|
$4.00 M |
- Support expert panels to develop consensus criteria for using imaging results as endpoints in clinical trials.
|
$0.20 M |
| TOTAL |
$6.2 M |
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| Objective 3: Increase clinical trials of imaging methods and technologies. |
- Expand a large randomized clinical study of spiral computed tomography as a screen in the detection of lung cancer, if initial data show a larger study is needed.
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$20.00 M |
- Initiate clinical studies to: compare CT colonography (virtual colonoscopy) with endoscopic colonoscopy for early detection of colon cancer and polyps in a large multi-institutional setting; evaluate magnetic resonance spectroscopy for the early detection and assessment of prostate cancer; and evaluate the role of FDG-PET studies for monitoring tumor response to therapy.
|
$4.00 M |
- Support corollary imaging studies, such as monitoring response to therapy, with 10 funding supplements to Clinical Trials Cooperative Groups.
|
$4.00 M |
- Support the development of the tools and infrastructure for the use of functional and molecular imaging in conjunction with radiation therapy, using novel treatment approaches including intensity modulated radiation therapy.
|
$2.00 M |
| TOTAL |
$30.0 M |
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| Objective 4: Accelerate the development and clinical testing of image-guided interventions. |
- Use 6 to 10 funding supplements to enhance programs such as the SPOREs for image-guided therapy research that emphasizes a problem-solving, organ-specific approach and promotes interactions between clinicians and bioengineers.
|
$3.00 M |
- Increase collaborations between the other Clinical Trials Cooperative Groups and the American College of Radiology Imaging Network (ACRIN) for testing promising, minimally invasive, image-guided interventions with four to six funding supplements.
|
$2.00 M |
| TOTAL |
$5.0 M |
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