Diamonds, gold and other materials are helping to fuel new breakthroughs in medical nanotechnology for the imaging diagnosis and treatment of cancer patients, according to research presented at RSNA 2012.
Nanotechnology is based on the use of particles that have one or more dimensions measuring 100 nanometers or less. These nanoparticles have a greater surface area per weight than larger particles and are more reactive to some imaging agents and chemotherapy, making them a valuable asset in the burgeoning field of theranostics, the integration of therapeutic and diagnostic medicine.
For example, gold nanoparticles have the potential to detect individual cancer cells circulating in the blood and destroy them with a laser, said Vladimir Zharov, Ph.D., D.Sc., of the Winthrop P. Rockefeller Cancer Institute at the University of Arkansas for Medical Sciences in Little Rock. Instead of drawing blood to look for cancer cells, clinicians could attach gold nanoparticles to biological molecules specific to cancer cells and inject them into the patient. Once attached to cancer cells, the gold nanoparticles could be seen with a laser beam and ultrasound transducer.
“If one single tumor cell passes the laser beam, it would produce an acoustic wave visible with conventional ultrasound technology,” Dr. Zharov said. “The same laser could be used to create transient nanobubbles due to water evaporation around nanoparticles to physically kill the cancer cells.”
Additional attachment of conventional drugs to gold nanospheres—now in Phase II clinical trials in humans—provides enhancement of antitumor action of this new so-called phototothermal nanodrug whose mechanism is based on synergy of laser-activated thermal, microbubble and biochemical-associated phenomena, Dr. Zharov said.
Dr. Zharov is particularly excited about the potential of gold nanoparticles to predict the establishment of metastases—the source of 90 percent of cancer deaths.
“Conceivably, the test can be used to determine the aggressiveness of cancer based on the numbers of tumor cells circulating in the blood,” he said. “By counting the number of cancer cells, we can also predict treatment and see if drugs work or not in real time.”
Researchers are experimenting with various nanoparticles for different imaging applications. At the University of California, Los Angeles, Dean Ho, Ph.D., and colleagues have been studying nanodiamonds—inexpensive, carbon-based particles made from the byproducts of mining and refining. Their multifaceted shape makes them ideal for binding with imaging agents and drugs.
“You can load imaging agents like gadolinium onto nanodiamonds,” Dr. Ho said. “Because of the surface facets, nanodiamonds attract water and you get a striking increase in imaging contrast efficiency.”
Nanodiamonds could also improve the effectiveness of chemotherapy drugs like doxorubicin.
“Many tumors are resistant to drugs because the cancer cells pump the drug out,” Dr. Ho said. “Nanodiamonds bind the drug so tightly, it gets stuck in tumor cells longer.”
Recent research highlights the potential of nanodiamonds to significantly reduce toxicity associated with chemotherapy. In a recent study on mice published in Science Translational Medicine, Dr. Ho’s group found that when they bound nanodiamonds to doxorubicin, the mice not only survived what had been a lethal dose, their tumors shrunk as well.
“Nanodiamonds further increase the efficacy of the drug,” he said. “This could make it possible to get the same effects from a lower dose.”
The research team is studying the technology in larger animal models with a push toward additional pre-clinical studies.
James R. Heath, Ph.D., from the California Institute of Technology in Pasadena, Calif., and a pioneer in nanotechnology, discussed protein catalyzed capture (PCCs) agents, a class of diagnostic and therapeutic agents that can mimic antibodies by reacting to surface areas of antigens known as epitopes.
“PCCs are a potentially powerful tool that are easy to manufacture and can be optimized for reaction with specific epitopes,” he said.
Session moderator Damian E. Dupuy, M.D., from Rhode Island Hospital and Brown University in Providence, R.I., said that nanotechnology lends itself to collaborative efforts among physicians, engineers and experts from other disciplines—a phenomenon commonly known as translational medicine.
“Lots of big cancer research hospitals are looking for new ways to diagnose and treat cancer and we’ll see more and more of these agents in the future,” he said. “As radiologists, we are at the forefront of this research.”
At the end of the session, Dr. Dupuy asked the researchers if he would see these nanoparticles in clinical use in his lifetime. All three answered “yes.”
Silver line impregnation reduces the incidence of catheter related bloodstream infections (CRBSI) in both single and double lumen long term central venous catheters (CVC), according to presenters at RSNA 2012.
Stavros M. Stivaros, B.Sc.(Hons), M.B.Ch.B., F.R.C.R., Ph.D., a consultant neuroradiolgist and clinical scientist at National Institute for Health Research (NIHR) and a lecturer at the University of Manchester, U.K., summarized the study’s clinical applications, saying that, “central venous catheter related infections have significant impact on patient morbidity and, at worst, mortality, in cancer patients. In our patient cohort, silver impregnated lines reduced infection risk.”
Dr. Stivaros, also a research team member with The Christie, one of Europe’s largest cancer hospitals (also in Manchester), said the study was intended to assess whether the use of silver impregnation into the polymer of the CVC reduces CRBSI in the cohort of cancer patients undergoing chemotherapy. Dr. Stivaros, also head of the Biomedical Decision Systems Group at the University of Manchester, collaborated on the research with Hans-Ulrich Laasch, doctor of medicine, M.R.C.P., F.R.C.R., chief of intervention at The Christie and supervisor of the procedure team nurses.
Referred over 15 months for CVC insertion in the specialist cancer center, 1,002 patients were randomized to receive either a standard or silver impregnated catheter. Except for silver contained in the catheter polymer, both catheters were identical. Patient follow-up continued until line removal and all removed lines were sent for microbiological culture.
Of the 1,002 patients randomized, 981 patient follow-ups were evaluated. During the study, specialist nurses from the vascular access team placed 488 standard lines (393 single lumen and 95 double lumen) and 493 silver lines (390 single lumen and 103 double lumen). Of these, 175 catheters were removed for reasons of CRBSI, including 15.8 percent single lumen and 41.1 percent double lumen standard lines. In the silver impregnated group, the frequency of CRBSI fell to 9.7 percent single lumen and 35 percent double lumen.
A stratified log rank test was statistically significant between the silver and non-impregnated lines (p=0.001) with a type-specific hazard ratio of 0.6 (95 percent CI, 0.44, 0.81), Dr. Stivaros found. Given the competing risks for line removal, such as primary diagnosis and chemotherapy type, he examined the probability of having the line removed for CRBSI in an environment in which other reasons for line termination are operating using Gray’s test, which showed that the cumulative incidence of CRBSI line removal stratified by lumen type was also statistically significant, he said.
“Our study has significant impact in terms of patient morbidity and treatment completion,” Dr. Stivaros added. “As the additional cost for silver is approximately $50, extrapolating from this study, 1,000 patients all receiving silver impregnated lines would have had an additional $50,000 cost, but this would have saved $200,000 in additional CRBSI related costs, for a savings of $150,000.”
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