Smaller, Brighter Probe Designed for Molecular Imaging and Tumor Targeting

Researchers have developed a new generation of microscopic particles for molecular imaging, constituting one of the first promising nanoparticle platforms that may be easily adapted for tumor targeting and treatment in the clinic.

According to the investigators from Memorial Sloan-Kettering Cancer Center (MSKCC; New York, NY, USA) and Weill Cornell Medical College (New York, NY, USA), these particles are biologically safe, stable, and small enough to be easily transported across the body's structures and effectively excreted through the urine. It is the first time that all of these characteristics have been successfully engineered on a single-particle platform, called "C dots,” in order to optimize the biologic behavior and imaging properties of nanoparticles for use in a wide range of biomedical and life science applications. The investigators' findings were published in the January 2009 issue of the journal Nano Letters.

"Highly sensitive and specific probes and molecular imaging strategies are critical to ensure the earliest possible detection of a tumor and timely response to treatment,” said the study's senior author, Michelle Bradbury, M.D., Ph.D., a physician-scientist specializing in molecular imaging and neuroradiology at MSKCC. "Our findings may now be translated to the investigation of tumor targeting and treatment in the clinic, with the goal of ultimately helping physicians to better tailor treatment to a patient's individual tumor.”

Imaging studies in laboratory mice conducted at MSKCC demonstrated that this new particle platform, or probe, can be molecularly customized to target surface receptors or other molecules that are expressed on tumor surfaces or even within tumors, and then imaged to assess various biologic characteristics of the tumor, including the extent of a tumor's blood vessels, cell death, treatment response, and invasive or metastatic spread to lymph nodes and distant organs.

"Importantly, the ability to define patients that express certain types of molecules on their tumor surfaces will serve as an initial step towards improving treatment management and individualizing medical care,” said Dr. Bradbury.

Many of the contrast agents or probes currently used in medical imaging (such as gadolinium diethylenetriaminopentaacetic acid [GdDTPA] for magnetic resonance imaging [MRI]) are not specific to any particular tumor type. According to the study's scientists, the data gained from imaging tumors targeted with C dots may eventually assist physicians in defining tumor borders for surgery, determining the extent of a tumor's spread, mapping lymph node disease, and improving real-time visualization of small vascular beds, anatomic channels, and neural structures during surgery.

Created at Cornell University and modified at MSKCC, C dots have been optimized for use in optical and positron emission tomography (PET) imaging and can be customized to any particle size without adversely affecting its fluorescent properties. For the first time, researchers were able to make them sufficiently small (in the 5 nanometer range) to remain in the bloodstream for a practical period and then to be efficiently excreted by the kidneys. Researchers were also able to increase their brightness by 300%, enabling cancer cells to be tracked for longer periods in the body.

The C dots'core is encapsulated in a shell of silica, a nontoxic element naturally found in fruits, grains, and vegetables, and contains optical dyes that emit light at longer wavelengths, resulting in an overall improvement in image quality compared to commercially available dyes.

Investigators also found that adding another type of molecular coating, called pegylation, protected C dots from being recognized by the body as foreign substances, thereby effectively extending the circulation time to improve tumor-targeting capabilities.

By comparison, first-generation nanoparticles, called quantum dots (Q dots), offer excellent brightness and provide good contrast during imaging, but their clinical potential is limited by their large size and risk of toxicity.

The scientists concluded that while the next generation of nanoparticles holds much clinical promise, more research remains to be done before C dots are approved for use in humans.

Related Links:
Memorial Sloan-Kettering Cancer Center
Weill Cornell Medical College