Researchers create smaller, brighter probe tailored for molecular imaging
Researchers have developed next-generation microscopic particles for molecular imaging that may be readily adapted for tumor targeting and treatment in the clinic, according to research that will be published in the January 2009 issue of Nano Letters.
According to the investigators at Memorial Sloan-Kettering Cancer Center (MSKCC) and Cornell University, both in New York City, these particles are biologically safe, stable, and small enough to be easily transported across the body's structures and efficiently excreted through the urine.
It is the first time that all of these properties have been successfully engineered on a single-particle platform, called "C dots," to optimize the biological behavior and imaging properties of nanoparticles, the researchers said.
“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, MD, PhD, 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 experiments in mice conducted at MSKCC showed that the 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 evaluate various biological properties 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.
Developed at Cornell University and modified at MSKCC, C dots have been optimized for use in optical and PET imaging and can be tailored to any particle size without adversely impacting its fluorescent properties. For the first time, researchers were able to make them small enough (in the 5 nanometer range) to remain in the bloodstream for a reasonable amount of time and be efficiently excreted by the kidneys. They were also able to increase their brightness by 300 percent, enabling cancer cells to be tracked for longer periods of time in the body.
The inner 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 dyes that are commercially available.
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, offer excellent brightness and provide good contrast during imaging, but their clinical potential is limited by their large size and risk of toxicity, according to the authors.
The researchers concluded that while the next generation of nanoparticles holds much clinical promise, more work needs to be done before C dots are approved for use in humans. They said that the information gained from imaging tumors targeted with C dots may ultimately 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.
The study was supported by a grant from the Clinical and Translation Science Center at Weill Cornell Medical College and the Cornell Nanobiotechnology Center.
According to the investigators at Memorial Sloan-Kettering Cancer Center (MSKCC) and Cornell University, both in New York City, these particles are biologically safe, stable, and small enough to be easily transported across the body's structures and efficiently excreted through the urine.
It is the first time that all of these properties have been successfully engineered on a single-particle platform, called "C dots," to optimize the biological behavior and imaging properties of nanoparticles, the researchers said.
“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, MD, PhD, 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 experiments in mice conducted at MSKCC showed that the 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 evaluate various biological properties 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.
Developed at Cornell University and modified at MSKCC, C dots have been optimized for use in optical and PET imaging and can be tailored to any particle size without adversely impacting its fluorescent properties. For the first time, researchers were able to make them small enough (in the 5 nanometer range) to remain in the bloodstream for a reasonable amount of time and be efficiently excreted by the kidneys. They were also able to increase their brightness by 300 percent, enabling cancer cells to be tracked for longer periods of time in the body.
The inner 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 dyes that are commercially available.
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, offer excellent brightness and provide good contrast during imaging, but their clinical potential is limited by their large size and risk of toxicity, according to the authors.
The researchers concluded that while the next generation of nanoparticles holds much clinical promise, more work needs to be done before C dots are approved for use in humans. They said that the information gained from imaging tumors targeted with C dots may ultimately 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.
The study was supported by a grant from the Clinical and Translation Science Center at Weill Cornell Medical College and the Cornell Nanobiotechnology Center.