“C Dots” Appear Safe for Use in Humans

Results from a first-in-human clinical trial suggest that a nanoparticle-based imaging technology known as Cornell dots (C dots) is safe for human use and may be more effective at mapping tumors than traditional radiotracers.

Invented by study co-author Ulrich Wiesner, PhD, professor of materials science and engineering at Cornell University in Ithaca, NY, C dots are organic silica particles 6 to 7 nm in diameter that encapsulate a fluorescent dye. Unlike other nanoparticles, such as liposomes, C dots are small enough to be renally excreted—avoiding toxic buildup in the liver—but large enough to stay in the body for at least 24 hours, unlike many small molecules.

After testing C dots successfully in human melanoma xenografts, researchers injected five metastatic melanoma patients with C dots coated with polyethylene glycol to ensure smooth passage through the kidney. Cyclic peptides, which target and bind to overexpressed integrins on tumor surfaces, were labeled with radioactive iodine to facilitate tracking with PET. Unlike quantum dots and other nanoparticles previously tested in animals, C dots produced no adverse side effects and cleared the body quickly. The results are published in Science Translational Medicine.

“This is the baseline study that establishes the safety and pharmacokinetics of using C dots,” says study senior author Michelle Bradbury, MD, PhD, associate professor of radiology at Memorial Sloan Kettering Cancer Center (MSKCC) in New York, NY. “Based on these results, the FDA is allowing us to expand the trial to other patients.”

The peptides' ability to bind directly to tumors suggests that C dots may eventually be developed for drug delivery, says Bradbury. Besides melanoma patients, investigators plan to test the imaging technology in patients with prostate, cervical, and uterine cancers.

“When you look at the PET image, you're looking at the actual amount of particles that accumulate at the tumor site, which is an indicator of how much of a drug-bound particle goes into the tumor over a period of time,” she says. “We may be able to use that information to decide how much drug needs to be delivered to the tumor for treatment, so that we're using the properties of the tumor to determine a safe dose rather than the weight of the patient—pointing the way to individualized patient care.”

C dots are also being employed to track the extent of disease in a more specific way, says Bradbury. A separate human trial now under way at MSKCC combines C dot fluorescence with a handheld camera, allowing surgeons to view a high-resolution image of tumor tissue and more selectively remove cancerous lymph nodes.

“The idea is to use PET imaging to map the disease before an operation and use optical imaging during the operation,” says Bradbury. “We are in the early stages with these kinds of platforms that can target tumors and help surgeons do a better job of removing diseased tissue.”