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For other articles and previous issues click here. June 13, 2005 Nuclear
Medicine’s New Molecular Image — An Interview With Society
of Nuclear Medicine President Mathew L. Thakur, PhD For decades, nuclear medicine has used radiopharmaceuticals to diagnose and treat disease. The field evolved along with the available imaging tools. Molecular imaging is a broad multidisciplinary field that combines state-of-the-art imaging with growing knowledge of molecular and cell biology to image (and ultimately treat) disease at the molecular/cellular level. It includes familiar nuclear medicine modalities such as PET and SPECT. Molecular imaging also utilizes MRI, ultrasound, and emerging technologies such as optical imaging. Mathew L. Thakur, PhD, is the president of the Society of Nuclear Medicine (SNM). He is also director of radiopharmaceutical research and nuclear medicine research and professor of radiology and radiation oncology and nuclear medicine at Thomas Jefferson University Hospital in Philadelphia. In 2002, the SNM changed its logo tagline to “advancing molecular imaging” to reflect this involvement. Thakur agreed to discuss how molecular imaging fits into the broader diagnostic imaging world that Radiology Today covers. Radiology Today: It seems that everywhere you look these days, you see articles discussing the promise of molecular imaging. Exactly what do you mean when you say “molecular imaging”? Mathew L. Thakur, PhD: Nuclear medicine has been doing molecular imaging for the past 50 years, so it’s not something new. It’s a new name and I think there is more excitement now for two reasons. One is that in nuclear medicine, radioactive tracers that we use will remain the mainstay of molecular imaging because these tracers allow quantitative and very sensitive ways of imaging. Second, more modalities have come into the field, such as MRI and optical imaging. You can use both for molecular imaging. Molecular imaging uses techniques that will directly or indirectly monitor and record the distribution of molecular or cellular processes for biological, diagnostic, or therapeutic applications. For example, if there is a cell and that cell is deformed by any chemical mechanism, it may eventually turn into a malignant cell. We can, using molecular techniques, detect that cell or cluster of cells and determine noninvasively what chemical modulations have taken place in that cell. The example I just used was for cancer; we can do a similar thing in neurology by monitoring the neurons, the beta amyloids, the plaques they form, and the receptors. We should be able to detect the process of Alzheimer’s disease or Parkinson’s disease very early in the process. RT: How, specifically, does molecular imaging detect the earliest stages of disease? Thakur: When that cellular modulation I mentioned takes place, the cells express on their surface certain molecules called receptors. Or, in the case of cancer, cells express genomic changes that are called oncogenes. Molecular imaging will allow us to probe those molecular events in a living cell without having to draw it out of the body. So while the cell is still surviving, we will be able to monitor those events inside it that will lead to the prediction or diagnosis of disease. We’ll be able to use similar processes to treat them as well. Suppose there is a cell in which we know that one of its genes has altered. We should someday be able to correct that gene as well. It will take a few years until this research can be used clinically at the bedside, but the processes are underway and there are good indications that it is going to be feasible. RT: So for the immediate future, we’re talking about diagnostics? Thakur: That’s right. I think that eventually we will call them molecular imaging and molecular therapy. But at the moment, there is more emphasis on applying this process for diagnostic applications. Eventually, the techniques will be applied to therapy as well, but we have to take one step at a time. These techniques are new and have some limitations that have to be overcome before we jump into deeper waters. RT: So developing molecular imaging agents for a broad range of diseases is the long-range promise of molecular imaging? Thakur: Eventually, every medicine we use for diagnostic or therapeutic applications will all be targeted at the molecular levels. To a certain extent, that is the case today, but in the future they will be more evolved to treat the molecular modulation within the patient’s body. It will be called molecular medicine. RT: When most Radiology Today readers think of imaging, they first think of anatomic imaging. And with the rise of PET, there’s much discussion about functional imaging. How do you differentiate them from molecular imaging? Thakur:We don’t want to compare apples and oranges. CT is based strictly on anatomy, not even the physiology. In anatomic imaging, which we have been doing for decades, CT can turn out to be sensitive and there can be some changes that it can determine, but molecular imaging—at least for MRI and optical imaging—is a new and evolving technique. Although people call PET molecular imaging, strictly speaking, most of it today is a metabolic imaging technique. PET detects cancer on the basis of metabolic activity in that tumor. The use of FDG [fluorodeoxyglucose]-PET, to my mind, is not truly molecular imaging. Fusion imaging simply puts together the two findings, like PET/CT. Fusion imaging gives the physician a precise location and depth of lesion by putting together the PET image and the CT image. PET is just going to show you a hot spot in the lung; it isn’t going to show you much of the surrounding bone [that] is there. CT is going to show the entire rib cage and the hot spot with a contrast agent. Putting the two together gives you the location of that lesion in an anatomically precise way to confirm that what you found with the PET imaging is the correct lesion. It gives the surgeon the precise anatomical location with respect to some other reference like the sternum or the spine. With molecular imaging, we mean to target a single cell. And in that cell, there are thousands and thousands of molecules. There’s the DNA, there are nucleotides, there are genes, there are chromosomes, and [there are] a number of different proteins. There are all kinds of molecules there. In molecular imaging, the whole modality is aimed at finding some abnormal process [at the molecular level] that will eventually lead to some kind of disease—maybe cardiovascular disease, maybe neurological disease, maybe oncological disease. The goal of molecular imaging is to target those abnormal molecules at the early state. You can target healthy cells with molecular imaging, but there are billions of cells in the human body. If they are normal, we are happy about that and don’t want to disturb them. But if out of those billions there are 1,000 cells that by some unknown chemical mechanism have changed their chemistry and begun to produce some new molecules—either within the cell or outside the cell—molecular imaging will target those abnormal cells and record their image on the screen. That will lead to diagnostic and, eventually, therapeutic application. By targeting I mean you need a probe—another molecule that to the end of which you can attach a radioactive tracer. When you inject that probe into the body, it will go and seek that particular molecule that we are targeting in that bad cell. Biology provides us the target in the cell. Then it is up to us to develop a molecule in a test tube and put a tracer on it, inject it into a patient, and let that probe find and bind tightly to those molecules on the bad cell, which then allows us to image that particular cell or cluster of cells. RT: Once you can find and mark those cells, is that when you look at issues such as treating patients earlier with existing techniques or, at some point, treating them with what you called molecular therapy? Thakur: Exactly. Right now, we don’t really know when a tumor forms. We don’t know how the metastatic lesion precisely happens. We don’t really know precisely the basic mechanism of it. By the time the patient presents in the clinic, certain tumors have grown too big or too advanced. For example, the most common screening that we do with imaging in the United States is mammography. We don’t do prostate imaging once a year, or whatever. So by the time the patients present, it’s often too late. Molecular imaging eventually will lead us to screening processes that identify this small cluster of abnormal cells in the body. We know that cluster will grow and we will say, ‘Let’s treat it now, either surgically, chemically, or radiologically.’ RT: What are the current key areas of molecular imaging research? Thakur: At the moment, most of the work focuses on these three diseases: cardiovascular disease, cancer, and neurological diseases. The molecular imaging process should also let you look into the early warning symptoms of diabetes, but we haven’t begun that work yet. Diabetes is another application that I think is of great interest. In the pancreas, there are certain cells called beta-islet cells—they are the ones that produce the insulin. In diabetics, for some reason, they don’t. Obviously, some changes occur in those cells. Right now we don’t understand why those changes occur, what kind of changes they are, and when they spread. That will be another area. Although diabetes is not regarded as a No. 1 killer, we have a large population of diabetic patients. Given the opportunity of time and funds, I would begin to look into those pancreatic cells.” RT: If disease state starts with disruption or change at the molecular level, eventually molecular imaging and therapy techniques could apply to every disease, at least those for which we don’t have a good treatment. Thakur: It is a growing area; work is being done every day. The biologists are doing a very good job. They tell us what goes on in the cells when certain things happen and what new molecules are produced. For us in nuclear medicine, we target those molecules. |
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