Medical Device Daily Washington Editor

WASHINGTON – The FDA's April 18-20 celebration of its 100th anniversary, titled “A Century of FDA Science: Pioneering the Future of Public Health,“ ongoing this week, is replete with retrospectives on the agency's success stories. But the bulk of the three days is being devoted more to the future – how the agency plans to address its mission both today and in times to come.

Nanotechnology on Tuesday found at least a small place in the break-out sessions, which number 23 for the gathering at the Washington Convention Center.

In an opening discussion of this emerging space, Igor Medintz, PhD, of the Center for Bio/Molecular Science and Engineering at the Naval Research Laboratory (Washington), gave a brief overview of the potential impact of and recent advances in quantum dots on medical imaging.

Alternately known as semiconductor crystals, these artificial atoms are also the subject of speculation as to their application in fields such as solar energy production and visual displays, and their potential utility in all these fields hinges largely on the unique chromatic behavior of quantum dots.

Medintz stated that the quantum dots he discussed were made up of between 100 and 30,000 atoms of various elements. He noted that the dots can emit near-infrared spectra, useful for medical imaging.

The reasons that quantum dots are superior to dyes for fluoroscopic imaging include that they offer a “high extinction coefficient“ (meaning, they are more persistent) and are more stable under chemical exposure. Quantum dots are also “orders of magnitude better“ than fluoroscopic dyes at holding up under exposure to light, according to Medintz.

The spectra of the emissions of quantum dots are dependent on the size of the dot, suggesting the possibility of manufacturing dots to specifications that offer more precise imaging possibilities than are currently available from fluoroscopic dyes. However, scientists will have to learn to control the number of biomolecules that attach to a dot and to ensure that they are properly oriented to make best use of a scan.

Medintz noted that “It is not a trivial matter to try to engineer the appropriate attraction“ of biomolecules to quantum dots.

Scott McNeil, PhD, the director of the Nanotechnology Characterization Lab (NCL) at the National Cancer Institute , offered some perspectives on the use of nanomaterials for diagnosis and treatment of cancer.

The lab is part of an effort called the NCI Alliance for Nanotechnology in Cancer , the aims of which are nothing short of ambitious. They include coming up with research tools to identify new biological targets and developing agents to monitor predictive molecular changes, and prevent precancerous cells from turning malignant.

The alliance also is working to improve on the current stock of imaging agents and diagnostics and to find “multi-functional targeted devices to deliver multiple therapeutic agents directly to cancer cells,“ according to McNeil.

Commencing with some well-known figures on fatalities and cancer epidemiology, McNeil remarked that more than 550,000 Americans will die of cancer this year and that about 1.4 million will get the bad news of a cancer diagnosis of one type or another.

He pointed out that despite the war on cancer, the death rate per thousand diagnoses remained essentially flat between 1950 and 2002 when the rates were 193.9 and 193.2, respectively. In that same span, the mortality rates per thousand for heart and cerebrovascular diseases fell from 586.8 to 241.7 and 180.7 to 56.5, respectively.

“Our progress in beating cancer is somewhat flat,“ McNeil observed.

The advantages of delivering anti-carcinogenic drugs via nanoparticles vs. conventional delivery schemes include the ability to deliver hydrophobic drugs, which is problematic in the watery human body, and the possible multi-functionality of nanoparticles in this pursuit. McNeil stated that nanoparticles can simultaneously serve the roles of detection and treatment of a cancer.

Thanks to these characteristics, nanoparticles may be able to reduce the toxicity and improve efficacy of conventional cancer drugs.

McNeil assured the audience that nanoparticles are “not just a fad. We're seeing great increases in efficacy“ with their use.

A recent experiment comparing the use of methotrexate in both conventional and nanotechnological delivery regimes served to buttress McNeil's point. He offered a slide that showed two albino lab mice, one of which had received the drug inserted in nanoparticles.

This rodent had substantial fur and achieved the same therapeutic index after only three milligrams per kilogram of body weight, a 10th of the dose needed to bring about the same effect in the other mouse, which was almost naked and was “lethargic.“ According to the slide, this experiment was performed by James Baker, MD, of the University of Michigan (Ann Arbor).

However, McNeil pointed to the several hurdles that researchers have to overcome before nanoparticle delivery of cancer drugs would arrive in clinical settings. One of these is a “critical lack of available standards“ and another is a “lack of understanding of the first principals of characterization.“ McNeil also lamented the lack of regulatory certainty in all this, but reminded the audience that the FDA is a partner in the alliance.

To get past these hurdles, NCL will work to “identify and characterize critical parameters related to nanomaterial biocompatibility“ and to develop a better understanding of structure-activity relationships, said McNeil. NCL also seeks to “establish and standardize an assay cascade for nanomaterial characterization,“ to examine the biological characteristics of “multi-component/combinatorial platforms,“ and to get industry and academia to work more closely in this endeavor.