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For example, Gore asks, “why take an agent targeting estrogen receptors if the tumor doesn’t have estrogen receptors?”
With molecular imaging, one could potentially “tag” probes that bind to particular receptors to see if a patient’s tumor expresses those receptors, and thus be likely to respond to drugs targeted to those receptors.
Perhaps the most promising application of molecular cancer imaging will be monitoring cancer response to therapy. These new methods are now possible because of advancements in understanding the biology of cancer.
“The big push in the last few years has been to develop better methods for assessing whether drugs are hitting their targets, and judging whether patients are doing well,” says Gore. “Our understanding of cancer biology will help us develop biomarkers of cancer response to treatment.”
Already, several Vanderbilt researchers are making progress in this area.
In November 2007, a multidisciplinary team of investigators including Gore, Hallahan, and Andrej Lyshchik, M.D., Ph.D., a Radiology resident, reported that “molecular ultrasonography” – ultrasound technology targeted to specific molecules – may enable in vivo imaging of biomarkers in tumor blood vessels, which could be used to evaluate early tumor responses to anti-angiogenic drugs.
In a mouse breast cancer model, they investigated the use of high-frequency ultrasound coupled with a contrast agent targeted to the vascular endothelial growth factor receptor 2 (VEGFR2), a receptor that is highly expressed in new tumor blood vessels and is a major target for several angiogenesis inhibitors.
They showed that the intensity of the ultrasound signal in the tumors correlated with the expression of VEGFR2, as confirmed by immunoblotting and histologic evaluation.
This technology, contrast-enhanced high-frequency ultrasonography, they wrote, “has several important advantages over other molecular modalities for in vivo imaging of angiogenesis.” It is portable, readily available, and is the only imaging modality that can provide real-time imaging. Ultrasound also is generally less expensive than nuclear imaging and MRI.
In addition to adapting technologies for molecular imaging, Vanderbilt researchers are also identifying novel molecular probes that may help individualize cancer treatments and speed up development of new cancer therapies.
Hallahan and colleagues recently developed a technique
that may be able to determine a cancer treatment’s effectiveness
within days of starting treatment instead of the weeks or months it currently takes.
“It currently takes two to three months of cancer therapy before we can determine whether the therapy has been effective for a patient,” says Hallahan. “If we can get that answer within one to two days, we can switch that patient to an alternative regimen very quickly.”
From a panel of billions of protein fragments, or peptides, Hallahan and colleagues identified one that specifically bound to tumors dying in response to a targeted therapy. To this peptide, they attached a light-emitting molecule and injected these labeled peptides into mice that had been implanted with human tumors.
Using specialized imaging cameras that detect light in the near-infrared range (invisible to the human eye), the investigators saw that tumors responding to therapy were “brighter” than non-responding tumors. The peptide detected response in a wide range of tumors – brain, lung, colon, prostate and breast – within two days of initiating treatment.
“The key word here is ‘days,’” Hallahan says. “This will allow us to minimize the duration of treatments with ineffective regimens in cancer patients.”
The next step will be to move the technology into humans. The imaging technique used in mice (near-infrared) is not sensitive enough to penetrate deeply into human tissues, so the researchers are adapting the technology to an imaging modality commonly used in humans, like PET.
Hallahan predicts that the peptide may enter clinical trials within 18 months. If the probe works as well in humans as it does in mice, he says, such molecular imaging methods could help accelerate the development of new chemotherapeutic drugs.
“In the pharmaceutical industry, we’ll have a patient on a drug for months before we can re-evaluate the size of the tumor,” Hallahan said. “If we can get that answer within a couple of days, it will speed cancer drug development in the early phases of clinical trials.”
This new frontier of molecular imaging holds much promise, but also faces major obstacles – not the least of which is funding.
“Funding is a real problem,” Hallahan notes. Federal sources of funding focus primarily on discovery research, but support for translating these discoveries into humans is scarce. Commercial interest is also limited since each kind of test may only be applicable in a small number of patients.
“There’s really a minimal amount of funding for that,” he says. “We have to make that road a little easier from discovery to application.”
Despite the roadblocks, Vanderbilt researchers will keep pursuing new avenues for viewing cancer’s march through the body.
“Imaging is a very useful tool,” Gore says. “You know exactly where you’re looking, how big it is. Imaging has a really persuasive message.” 
Find out more about Vanderbilt’s Institute for Imaging Science at www.vuiis.vanderbilt.edu.
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