Defining the Marketplace

The scope of molecular imaging is expanding. R&D efforts are making clinical inroads and the already invaluable tool for nuclear medicine and oncology applications is showing promise in cardiology and neurology applications. For patients, molecular imaging promises earlier, more accurate diagnoses as well as earlier, more effective therapy. To better understand what is on the horizon for molecular imaging, Health Imaging & IT spoke with Edward Coleman, MD, professor of Radiology, director of Nuclear Medicine and vice chair of the Department of Radiology at Duke University Medical Center, and president of the Academy of Molecular Imaging (AMI), about the current state and future of molecular imaging.

Coleman has published more than 400 scientific papers in several leading journals, authored 80 book chapters, and published seven textbooks on topics related to nuclear medicine. He has served as past chairman of the American Board of Nuclear Medicine, is a fellow of both the American College of Radiology and the American College of Chest Physicians, and is a member of the American Association for the Advancement of Science.

Q: From a clinical standpoint, what is the state of molecular imaging today and what technologies are used? What about the R&D pipeline?

A: Clinically, molecular imaging is almost entirely limited to nuclear medicine with both single photon and PET imaging. When one thinks of molecular imaging at this time, PET is the modality that is most widely considered a molecular imaging technique. FDG, the tracer that is most widely used clinically at this time, as well as new tracers that are being evaluated for looking at different biologic parameters of tumors, fall into the category of molecular imaging. There are some aspects of MRI that are being used today clinically and are considered molecular imaging, such as looking at oxygen metabolism.

From the research standpoint, molecular imaging technologies include SPECT, PET, MRI, magnetic resonance spectroscopy and ultrasound.

Q: How is molecular imaging going to change the way disease is currently diagnosed, treated and monitored?

A: It is going to have an increasingly important role. It is going to lead to earlier, more accurate diagnosis. And it's going to lead to earlier, more effective therapy. With some cancers and therapies, after one dose, PET can determine if the treatment is effective or not. Right now, for many of the cancer therapies, we are treating the patients for six weeks to three months with $50,000 to $100,000 worth of medication that frequently has side effects. We don't know until the end of that period whether that treatment is effective or not. Changing this is going to improve patient management tremendously. It will decrease healthcare costs, improve outcomes. And we can expect more progress in therapy monitoring, because what we are doing is the very tip of the iceberg.

Q: The projected molecular diagnostics market could reach $10 billion by 2007 (according to VisEn Medical). What will be the state of molecular imaging next year as well as in the next five and 10 years?

A: From a clinical standpoint, in the next year molecular imaging's not going to be a lot different than it is now.

In the future, I think a major use of molecular imaging is going to be similar to the way monoclonal antibody imaging is being used now, that is, as a precursor to monoclonal antibody therapy.

Molecular imaging will be used in the evaluation for the use of molecular therapies [the therapeutic agent will be radiolabeled as a diagnostic agent] to determine its distribution, localization and kinetics. Molecular imaging will be used as part of the pre-therapy analysis and following therapeutic effect. There will certainly be other ways to follow therapeutic effect by molecular imaging techniques. This is another big growth area that will be available by 2007. Ultrasound over the next five years will be complementary to molecular imaging, providing some anatomic information and potentially some flow information, but I don't see it having a direct impact on molecular imaging.

In 10 years, molecular imaging will be huge - almost all of imaging will be molecular imaging. It will be using a wide array of imaging techniques, some of which we may not even know of for sure yet. Some molecular imaging will be using SPECT and PET as it has progressed to by that time. Some molecular imaging will be using MRI or MR spectroscopy.

Q: While much R&D in the field of molecular imaging focuses on oncology, what is being explored in cardiovascular and neurological diseases, such as Alzheimer's disease?

A: A lot of the focus of molecular imaging and molecular medicine has been on cancer. But research is ongoing in molecular imaging of the brain and heart. The results of this research will come to fruition in the five to 10 year time frame.

In Alzheimer's disease, the pathologic changes that occur in the brain are being characterized and used to develop molecular imaging agents that would be used for the early detection of AD. For example, there is increased localization of amyloid in the brain in patients with AD. There are now tracers being developed that localize in components of amyloid, and these molecular imaging agents should be more sensitive and specific for the diagnosis of AD.

In other neurological diseases, there is certainly a lot of research ongoing characterizing the molecular defects of many diseases, such as Parkinson's disease, and imaging agents are being based on the molecular abnormalities in these diseases.

The same is true for cardiovascular diseases. A lot of work is going into the development of molecular markers of atherosclerosis. The role of cellular abnormalities in ischemic disease and infarction is an intense area of research, and the potential use of stem cell therapy to treat the myocardial damage is providing interesting results in animal models.

Q: Will molecular imaging play a role in decreasing the incidence of cardiovascular disease?

A: To start with, I think that molecular imaging is mainly going to improve treatment options. I think that the earlier detection and identification of disease is going to come through genomic analysis and determining who is at risk for disease. Eventually molecular imaging will play a role in the early identification of disease, but at first, it's going to be primarily oriented to patients who have evidence of the disease. Identifying the patients before they clinically manifest disease is going to be more difficult. That's further down the road, in my opinion.

Q: What is molecular imaging's role in radiation oncology?

A: Molecular imaging is being used in radiation oncology in academic medical centers. Its use is starting to trickle down to the large community hospital. Most radiation oncologists are going to be using molecular imaging and other functional imaging very soon, and in two or three years, it will be a standard of care. We are going to see PET/CT and MRI scanners in radiation oncology centers. Molecular imaging is going to expand the need for new technology into practices of radiation oncology that have not had this new technology in the past.

Q: What progress has been made with molecular imaging agents?

A: Not a lot of progress as far as molecular imaging agents used in the clinics. But much progress has been made in the laboratory, and some of that progress has been moved into animal models. There are several agents that are in the pipeline that will be molecular imaging agents. One of them is the fluorine-18 l-thymidine for characterizing cell turnover. This agent is being used in several research centers, and I think that will be used clinically in the next three to five years. Another molecular imaging agent is fluorine-18 fluorocholine that has shown to be accurate in identifying cancer in the prostate gland as well as spread of the cancer. Presently, there is not a good way to image prostate cancer, and this agent looks very promising. There are two to three AD agents that are out of the laboratory into clinical research. These agents will help us to better understand the disease as well as make an earlier diagnosis.

I think the big area of molecular imaging in the next few years will be the development of new molecular therapies for cancer and using radiolabeled tracers of those agents to determine if the molecular therapy does get to the tumor and the effectiveness of this molecular therapy.

Q: What imaging techniques are utilized and being improved to explore the biological processes underlying disease?

A: PET is being used to characterize the biology of cancer. The big advance in PET has been the combination of PET/CT. PET scanners provide better resolution so we can identify smaller lesions. If molecular imaging of the brain continues to go well, there will be the development of devices in PET that will have higher resolution and be for evaluating the brain only. Presently, we use one scanner for both the brain and body. I think that we are going to see dedicated PET and SPECT devices for breast imaging, too. We will be evaluating some of these molecular probes to determine if breast cancer is present of not, and then if so, whether or not treatment is effective.

With MRI, we are going to see better resolution and faster imaging speeds as we go to higher field strength magnets. We are at 3T and where we go from there is still to be determined. MR spectroscopy is better with the higher field strengths.

In ultrasound, there is an interest in using microbubbles, and possibly some molecular information can be obtained using liposomes with ultrasound, but that is very much in its infancy.

Another area is optical imaging. The problem with the use of optical imaging is the penetration of light is very limited. But in some areas, such as esophageal cancer which involves the lining of the esophagus, for the early detection of cancer we will be able to inject molecular imaging agents that will fluoresce and localize optically. Endoscopy could be used to determine whether a molecular agent specific for cancer is present using optical techniques. Possibly in the breast there may be enough penetration of light to be able to use optical imaging to evaluate the breast. The problem with optical imaging is once a lesion gets very deep, light cannot penetrate deeply enough.

Q: How will the implementation of digital imaging and information management systems - as well as digital storage and archiving systems - throughout the healthcare enterprise impact molecular imaging and its inclusion in clinical practice?

A: Certainly the images that we now generate are important to the clinicians taking care of the patients. The referring physician not only reads a report, but wants to see the images and have the images available to show the patient. IT is going to be a major component if molecular imaging is to really have its full impact. There is going to be the need to have image manipulation readily available. For example, we are going to need to put the information from optical images on anatomic images along with other molecular information. The ability to combine the information [and some of this is large amounts of data], and then being able to move the information, is going to be extremely important to medical care in the future.

Q: What is the state of molecular imaging and genomics? How will the two benefit future patient care?

A: I do think molecular imaging will be incorporated into monitoring gene therapy. This is being done in animal models where gene therapy is being used and molecular imaging being performed with PET to follow the distribution of the genes and whether they are functioning. I think that we will see other aspects of PET used in evaluating gene therapy.

Q: What position do both the Food and Drug Administration and Medicare take on molecular imaging? Has this improved recently? Will it get better in the future?

A: The FDA is struggling to know how to evaluate these molecular therapies as well as molecular imaging agents. There is a meeting this month at the FDA to talk about molecular imaging, focusing primarily on PET imaging. The discussion will include how molecular imaging agents are initially evaluated in patients and then how those agents are approved by the FDA. The FDA is seriously looking into the development of molecular imaging agents and the changes needed to be made to facilitate the evaluation of these new agents.

Medicare is going to be receptive to using molecular imaging probes once they are shown to be not only safe and effective but also to have clinical applicability by providing information that is equal, if not better, than that from other techniques that are now available.

Q: Is one of the goals of molecular imaging to have noninvasive in vivo imaging as an alternative to biopsies and pathology slides?

A: Absolutely. I think that molecular imaging is going to provide noninvasive information equivalent to a biopsy. As these molecular imaging agents get developed, they will be more sensitive and specific than what we have now and compete with biopsies and tissues samples. In the future, we will have these molecular probes that will tell us by the images the information [we need] about the tissue. We won't need to do nearly the number of procedures that we do now to characterize what is actually going on.

Q: What milestones have already been obtained in molecular imaging?

A: I think one was the radiolabeling of glucose to develop F-18 fluorodeoxyglucose. That is the major molecular agent in use today and it's being used in 700,000 to 800,000 patients this year.

A second outstanding development for molecular imaging has been the combination of PET/CT to give better diagnostic information, more sensitive, more specific information than we have had in the past.

Q: What is needed to push molecular imaging to obtain these future goals?

A: What we need are probes that will provide greater specificity. We need the molecular biologists to provide us specific probes that will tell us not only if this is cancer but the type of cancer, as well as probes that will tell us that this molecular therapy is going to the tumor and the molecular therapy will be effective.

Q: What is patient care going to be like in the future with molecular imaging?

A: Many biomarkers will be developed for screening from blood samples. When a patient has a biomarker that is abnormal, then there will be a molecular agent that will be administered to see why that biomarker is abnormal - where is the abnormality in the body that causes the biomarker to be in the patient's blood. That will very likely be the precursor for the treatment. We may get to the point where we don't even need to know where it is, but I certainly think that imaging will play a role for a long time to determine the location of the abnormalities and will help guide the therapies.

Q: For a child born 10 years from now, how will his healthcare differ from a child born today?

A: It's going to be a lot different. We are going to be able to diagnose diseases much earlier by evaluating the genome. From a sample of tissue, we will have a good idea what diseases the child is likely to develop. For example, sickle cell disease, cystic fibrosis and some of the other genetic diseases that now lead to the early demise of the patient will be detected and treated effectively at an early age. I think in the next 10 to 20 years there will be "maps" that will be able to determine if a child has some of these serious genetic diseases. Furthermore, there will be genomic patterns that will tell us the therapies that will be effective and not effective. Individualizing therapy in the future will be possible by knowing the genome of the patient.