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The problem of registration can be overcome by combining two different imaging modalities into a single apparatus. This allows researchers to simultaneously obtain a tumor’s physical measurements as well as information about the molecular processes going on in the tumor. Already, combined imaging is making an impact on cancer diagnosis and treatment in humans.
“Combined imaging is going to be big,” says John Gore, Ph.D., director of the VUIIS and Cancer Center member. “These hybrid instruments will be able to give you information simultaneously. You’ll be able to get physiological measurements, anatomical measurements, as well as molecular imaging information.”
For example, PET-CT, which is already in clinical use, has been one of the great advances in cancer imaging. The PET scan detects glucose metabolism, which tells the physician whether a growth within the body is cancerous or not (malignant growths metabolize more glucose than benign tumors). CT provides detailed information about the size, shape and location of the tumor but cannot differentiate malignant lesions from normal or benign lesions as accurately as PET. Gore predicts that more types of combination imaging are on the horizon from MRI-PET to SPECT-CT.
Vanderbilt researchers are continuing to refine the existing platform of MRI for cancer monitoring. One advancement, called dynamic contrast-enhanced MRI (DCE-MRI), is already being tested in women to determine the effectiveness of targeted therapies in shrinking breast tumors.
DCE-MRI is a “general technique to look at blood flow and
vessel permeability in tumors,” explains Yankeelov, who conducted his graduate studies on the technology. “It’s well known that a tumor can’t survive on its own after it gets to be about a cubic millimeter. It has to vascularize (grow new blood vessels), in this well-known process called angiogenesis.”
“Angiogenesis inhibitors” make up a large segment of recently developed targeted therapies, but their clinical effectiveness needs to be monitored over the long-term. DCE-MRI may be a way to observe if these drugs – which include Avastin and Sutent – are having their intended effect of preventing angiogenesis.
Vessel development inside a tumor is “very chaotic,” says Yankeelov. These vessels are not normal – they are leaky and unstructured. “DCE-MRI is a way to probe that leakiness to see how tumors respond to these anti-angiogenesis drugs, and do it non-invasively over time,” he says. “It’s a very useful tool. But it’s not a magic tool that tells you everything you need to know about a tumor.” It will, he says, need to be combined with other measures of cellular proliferation and other molecular features of the tumor.
Going molecular
Molecular imaging, or imaging based on advancements in basic molecular and cellular biology and genetics, is one of the most exciting and promising new avenues for imaging.
VUIIS and Cancer Center scientists are working to develop novel molecular imaging methods, including molecular probes that can reveal aspects of tumor behavior.
“Part of the thrust in cancer imaging now is, can you target treatment knowing more about the tumor?” says Gore. “Characterizing the tumor more completely is important especially for first-line medicine. And that’s one thing that imaging will be able to do quite well.”
Molecular, functional and metabolic imaging has the potential to reveal physiologic, cellular and molecular processes related to disease. These include glucose metabolism, blood flow, oxygen use, cell proliferation rate, and alterations in gene expression and intracellular signaling pathways that influence tumor behavior.
Such techniques may find uses in early diagnosis by detecting changes happening at the cellular or molecular level that appear before the onset of symptoms.
Recently, Cancer Center member Robert Coffey, M.D., and Vanderbilt chemistry professor Darryl Bornhop, Ph.D., reported their development of novel fluorescent ligands of the peripheral benzodiazepine receptor (PBR), a membrane protein whose expression is increased in colon, prostate and breast cancer. Using this ligand, which was tagged with a fluorescent (light-emitting) compound, the researchers were able to detect early stage colon tumors in mice genetically predisposed to developing colon cancer. The probe also accurately distinguished the tumors from inflammation – key to developing a sensitive and specific screening test for cancer.
“The ability to follow molecular events in vivo represents a
paradigm shift for medical science,” they wrote in their April 2007 paper reporting these results. “A critically important goal of molecular imaging studies is to detect spontaneously arising tumors in the context of the host/tumor microenvironment.”
This particular molecular imaging tool will facilitate rapid cancer screening in animal models. But the researchers are also working to adapt the technology for human use by labeling the probes with radioactive compounds for use in existing clinical platforms, like SPECT and PET, with the long-term goal of improving the early diagnosis and therapy monitoring in colon cancer.
“Additionally,” they wrote, “we expect these agents to be useful for noninvasive monitoring of therapeutic efficacy that should be useful in improving clinical outcomes.”
Molecular-based imaging may also allow physicians to determine, based on the tumor’s molecular characteristics, which targeted treatments would be most likely to work in a particular patient.
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