Near-Infrared Nanoparticle Imaging Technology Developed for Breast Cancer Detection

Current imaging methods, such as X-rays and magnetic resonance imaging (MRI), are limited in the size of tumors they can detect, the depth they can penetrate the body, and by their potential side effects. Another promising imaging technique, NIR bioimaging, is a noninvasive, painless, and nonionizing form of radiation that operates at wavelengths just above that of visible light. By combining NIR imaging with nanoparticles containing indocyanine green, a NIR fluorescing dye, researchers from Penn State Milton S. Hershey Medical Center (Hershey, PA, USA) and Penn State College of Medicine and the departments of materials science and engineering and physics were able to detect breast cancer tumors 5 mm in diameter in a live mouse model over a period of four or more days.

Indocyanine green is the only NIR organic dye approved by the U.S. Food and Drug Administration (FDA) for use in the human body. The nanoparticles, which are approximately 20 nm in diameter, are made of calcium phosphate, a biocompatible material that has long been used as a bone replacement. Unlike other nanoparticles considered for imaging and drug delivery (e.g., semiconductor quantum dots), the biodegradable components of calcium phosphate nanoparticles are already widely present in the bloodstream.

In addition to the combination of near infrared imaging and nanoparticles, a second innovation is the development of a fundamentally new method for processing nanoparticulates. The process is called van der Waals HPLC (high-perfusion liquid chromatography). Materials scientist Dr. Jim Adair, whose team synthesized the particles, stated, "Our technique takes advantage of the large van der Waals forces associated with particles, as opposed to the small van der Waals forces associated with molecules, atoms, and ions. The hard part in the synthesis was making sure the particles did not clump together. The critical stage was the laundering of all the nonessential byproducts associated with the synthesis. By the end, we had a very clean suspension of particles in which all the spectator ions, molecules, and atoms had been washed away from the basic nanoparticles.”

The Penn group, led by pharmacologist Mark Kester, showed that their nanoparticles provided the fluorescent dye with 200% greater photoefficiency compared to indocyanine green injected into the bloodstream, with a 500% greater photostability. In a separate experiment discussed in the study, the researchers were able to image through 3cm of dense pig muscle tissue, which should correlate to at least 10 cm, and likely much deeper, in patients, according to Dr. Adair.

The study was published in the September 19, 2008, on-line issue of the journal ACS Nano.

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Penn State Milton S. Hershey Medical Center