Profiles in Cancer Research
This article is part of a series of stories related to new technology in cancer research. You can read more articles in the series here.
Dr. Samuel Achilefu
Director of the Optical Radiology Laboratory and Professor of Radiology,
Biochemistry & Molecular Biophysics, and Biomedical Engineering
Washington University in St. Louis, MO
Growing up in Idah, Nigeria, a small city on the Niger River, Dr. Samuel Achilefu was advised by his parents that the best way to make a difference in the world is to pursue higher education. And, as a young boy, he was inclined toward the nuts-and-bolts side of science.
“I was always curious about how things worked, and I enjoyed mathematics and statistics,” he recounted recently. “For a time, I thought that solving equations could solve all the problems of the world. It wasn’t until I took chemistry and biology in college that I realized that to have an opportunity to make a real difference to people, you need to get into the laboratory.”
Today, Dr. Achilefu runs a 35-person research laboratory dedicated to pushing the boundaries of optical imaging to meet the requirements of modern molecular medicine. Optical imaging can be broadly defined as the use of light to visualize an object. A simple light microscope, the staple tool of high school biology classes, is an example of an optical imaging technique. So is a modern digital imaging system that can detect a fluorescent probe attached to a single cell—or even a single molecule within that cell.
Even with the widespread availability of nonoptical technologies such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) in hospitals and laboratories, researchers remain interested in improving optical imaging technology for three main reasons. First, the equipment required is relatively inexpensive. Second, optical techniques use no ionizing radiation. (Radiation exposure from medical imaging has become a concern.) And finally, optical imaging provides exquisite resolution. Powerful optical cameras can capture the presence of a molecule at extremely low concentrations, down to one trillionth of a mole (a unit of measurement used in chemistry to express the amounts of a chemical substance).
Until recently, the unfortunate trade-off for this resolution has been very limited depth. Traditional optical techniques can penetrate only about a few micrometers into living tissue. After that, the light waves start to scatter, producing an unreadable picture. Dr. Achilefu and his team at Washington University's Optical Radiology Laboratory are exploring new ways of breaking that depth barrier so that optical imaging can have a larger role in cancer diagnosis and treatment.
From Academia to Industry—and Back
After completing his initial training at the University of Ibadan, Nigeria’s premier university, in 1987 Dr. Achilefu received one of five prestigious French government scholarships issued to promising young students from Nigeria. He chose to study materials chemistry and biochemistry and earned his doctoral degree at the University of Nancy in France. Next, he went to Oxford University to do postdoctoral research on how oxygen is transported through the body in the bloodstream and on the development of blood substitutes.
He had initially hoped to stay on a straight career path in academia. Instead, he ended up on a nearly decade-long detour into industry. At the end of his postdoctoral work at Oxford, his mentor was recruited to lead a new research department at Mallinckrodt Medical, Inc., headquartered in St. Louis, MO, and he convinced Dr. Achilefu to come with him.
“My tenure there was very advantageous,” said Dr. Achilefu. “Companies are more interested in patents, not necessarily scientific publications like in academia, and the patent process taught me to always ask a simple question: ‘So what? After you’ve done whatever you want to do in the lab, what will be the impact on the people you’re trying to help?’ I got used to always thinking about the direct impact of whatever research I do.”
At Mallinckrodt, Dr. Achilefu continued to work on oxygen transport, developing systems to help deliver oxygen to the lungs of newborns with respiratory distress syndrome. The efficiency with which the molecule hemoglobin delivers oxygen throughout the body made him wonder if the delivery of molecules on the molecular level could be used to image biological processes in the body.
“In the 1980s, there was no such thing as molecular imaging as we know it today,” he remembered, “but people were thinking about it; there was a wave of curiosity. Then the first peptide-based targeting agent was approved by the FDA in the early 1990s to detect neuroendocrine tumors.” That compound, called OctreoScan, used a radionuclide, exposing patients to a small amount of radioactivity during testing. “I wanted to know if we could do the same thing without using ionizing radiation. That curiosity was what led me into optical molecular imaging,” he explained.
Near-Infrared Probes See Further
In 2001, with almost a decade of experience in optical imaging research, Dr. Achilefu returned to academia at the Washington University School of Medicine. In 10 years, he has expanded the Optical Radiology Laboratory from one full-time researcher—himself—to a 35-person multidisciplinary team with expertise ranging from biomedical engineering and medical physics to chemistry, biochemistry, and immunology. “We really believe in multidisciplinary research, and that draws a lot of people here,” he said.
Their current focus in cancer research is on developing chemical and biological imaging probes that can be used to visualize their target with near-infrared light. Near-infrared light has a longer wavelength than visual light, allowing it to travel deeper into tissue. “The exciting thing we’re doing now is taking this technology into intraoperative procedures to identify tumor margins in places that surgeons would normally have a difficult time seeing with the naked eye,” he said.
His team has constructed a prototype goggle system that would allow a surgeon to identify near-infrared fluorescence in tumor tissue during surgery, without having to stop and look at images captured by a camera. The goggles also have the capacity to broadcast what the surgeon sees over the Internet in real time for telemedicine applications.
After receiving positive feedback from researchers around the world on their proof-of-concept study published last May in Surgery, the team is shrinking its prototype and refining the goggles to give surgeons binocular, three-dimensional vision, with the aim of testing it on human cancers.
In another, NCI-funded project, the team is pairing near-infrared probes with endoscopy. Their current probes can see about 2 cm into the body—a depth that can provide useful anatomical information when used endoscopically or with a catheter in the gastrointestinal tract or cervix, for example. Between endoscopy and catheterization, “a significant percentage of procedures done in hospital[s] today are amenable to optical imaging,” explained Dr. Achilefu. He and his colleagues plan to test the new probe for improving the removal of polyps and small tumors in the colon during endoscopic surgery.
The team also has NCI funding to test whether photoacoustic-based multimodal imaging, which uses optical technology and sound to pinpoint cancer cells, could improve upon traditional sentinel lymph node biopsy for breast cancer. This project, in partnership with Dr. Lihong Wang, director of the Optical Imaging Laboratory at Washington University, is testing a near-infrared probe to see if tiny deposits of cancer cells in the axillary lymph nodes could be detected with imaging alone, eliminating the need for surgical removal of suspected sentinel nodes.
In the future, Dr. Achilefu and his team hope to use their probes to monitor cancer treatment at the molecular level—for example, to see within hours of administration whether a chemotherapy drug is reaching and affecting cancer cells. “Today, we have to wait for weeks or months, because we’re looking for structural changes [in the tumor]. We believe optical imaging would be able to provide that information within 24 hours, and that it will be predictive,” he proposed.
Dr. Achilefu remains as excited about the potential of optical technology as he did as a newly minted scientist, watching the birth of its use in molecular imaging. And he stays inspired by his students who feel the same way. “Young people are really excited about this technology, so that’s why I’m happy about the future of our optical imaging work,” he said.