After the removal of a malignant tumor, both cancer surgeons and patients often wonder if the procedure successfully removed all of the disease. It takes just one cancer cell to spur a recurrence, and with conventional imaging technology offering a limited view on where cancer cells may be hiding, surgeons frequently resort to taking out healthy tissue as a precaution.
"For certain cancers, the best chance for a cure is to cut it out, but conventional pre-operative imaging can't show the surgeon precisely where the cancer ends and the healthy tissue begins, so there's always an element of uncertainty," said Chadwick Wright, MD, PhD, an assistant professor of radiology at The Ohio State University College of Medicine.
In an effort to increase the precision and reduce the anxiety of cancer surgery, Wright is developing a hybrid imaging agent that has both the benefits of pre-operative nuclear imaging, plus the ability to make cancer cells "light up" during the procedure. When viewed on a video screen through a special camera, the glowing cells provide surgeons with a real time visual of cancer cells, enabling them to make more precise excisions and confirm that they've adequately cleared the surgical site of all detectable malignant tissue.
"This type of imaging agent could go a long way to help reassure patients and surgeons," said Wright, who won a Davis Bremer pilot award from Ohio State's Center for Clinical and Translational Science (CCTS) to develop the agent. "Ultimately, we hope it could also help lower the risk of recurrence"
"Unusual' peptide homes in on tumor cells
Wright's imaging agent is designed around a peptide called HN1, which was first discovered about 15 years ago by scientists studying head and neck cancers. HN1 has such a strong affinity for this tumor cell type that it's been called a "head and neck cancer homing device."
Wright learned about HN1 while attending a brainstorming session held by Ohio State chemist and imaging scientist Michael Tweedle, PhD, who regularly gathers cross-functional researchers and physicians to discuss ways to translate clinical need into innovative treatments. Tweedle had been working with Theodoros 'Ted' Teknos, MD, Chair of Ohio State's Department of Otolaryngology and Quintin Pan, PhD also with the Department of Otolaryngology, who had successfully attached a tumor-killing treatment to HN1 in previous research. Tweedle says that HN1 was a hot topic among the group because it had unusual qualities that made it seem like an ideal diagnostic and therapeutic candidate.
"Peptides can be great vehicles to deliver drugs right where you want them, but many can only carry one type of compound, or are too big to target cancer cells efficiently," said Tweedle, who is Wright's CCTS mentor and Professor and Stefanie Spielman Chair in Cancer Imaging at Ohio State's Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. "HN1 is unusual in that it tolerates being labeled by a large chemical and still demonstrates the ability to target cancer cells."
Engineering the perfect combination
While the team felt that HN1 had potential as a hybrid imaging agent, it was Wright who suggested the formula: a radioactive isotope more commonly used in cardiology imaging coupled with a near-infrared dye.
According to Wright, dual probes are exciting new concepts that have gained momentum as scientists try to combine the best features of traditional nuclear and fluorescent optical imaging.
"Fluorescent dyes can fade quickly and be blocked by normal tissue, but provide a real-time, detailed view. Medical radioisotopes don't give you the detail you want, but are invaluable measurement tools," says Wright, who is also part of an Ohio State research team developing a novel radioisotope-based dual probe. "An effective dual probe has to combine the best attributes of current imaging agents while leaving out undesirable traits."
For HN1's payload, Wright is using an infrared dye that appears better suited for fluorescence imaging during surgery, and an attachable medical radioisotope that is small enough to fit on the peptide. Wright came up with several variations of the peptide so that the team could identify the most promising candidates.
Dual probe may unlock therapeutic, technology possibilities While HN1 has shown an affinity for other types of cancer cells, the compound is initially being developed for use in head and neck cancers, where preserving tissue is a top priority.
"Surgery to remove head and neck cancers can be particularly disfiguring, so having a dual probe that can help improve our precision would advance treatment significantly," said Teknos.
Teknos says that Wright's findings have implications from a therapeutic standpoint as well.
"Until now, we haven't had a way of measuring how much therapeutic HN1 can deliver into a tumor. With Dr. Wright's successful fluorescent and isotope labeling we can finally do that, making HN1 a more viable cancer treatment candidate," said Teknos. "It's a great example of how Ohio State, as a living laboratory where researchers share and collaborate, is helping accelerate discovery and improve patient's lives."
Wright says that figuring out the chemical add-ons that turn HN1 into a dual probe is just the beginning of the making it a functional diagnostic. The research team is currently testing different derivatives of the molecule. The team plans to move to testing in animal models in the next year, with the goal of having a potential imaging agent available for human testing within 5 years.
Wright hopes his advancements will also help spur innovations on the imaging hardware side.
"If I'm dreaming really big, maybe someday Google Glass will be powerful enough to stream real time images to the surgeon, or we'll have technology that can superimpose the image onto the actual surgical site," Wright said.
Materials provided by Ohio State University Center for Clinical and Translational Science. Note: Content may be edited for style and length.
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