Medical Device Daily National Editor
"It would be good if you could just inject something and see what a patient has," says Michelle Bradbury, MD, PhD, a researcher at Memorial Sloan-Kettering Cancer Center (MSKCC; New York).
And she says that the "next big thing in imaging is that the probes that we have and contrast agents we have really need to go to the next generation" and that the work in this areas has been "trying to trend that way."
In a conversation with Medical Device Daily, she says that the work she is pursuing in order to achieve both of these goals, though "almost science fiction," could be available in three to five years.
Bradbury is senior author of a study describing the development of a new type of nanoparticles, called "C dots," which she says could form the basis for new imaging agents that can better target the type of cells forming a cancer tumor and thus provide a path to real personalized drug treatment in oncology and other diseases.
Developed by the MSKCC researchers in collaboration with Cornell University (Ithaca, New York), these particles – called "C dots," to signify their initial creation at Cornell – are biologically safe, stable and small enough to be easily transported across the body's structures, then excreted through the urine, according to Bradbury.
She says that C dots are distinguished from the molecule called a quantum dot (Q dot) which is the basis for most current imaging agents. Many of these agents, such as GdDTPA used with MRI, can't clearly differentiate different types of cancers. This lack of differentiation, Bradbury says, means treatment too often is "one size fits all."
And while drug developers are producing more targeted drugs for specific populations and diseases, the determination of exactly what target, or targets, these drugs should focus on is rarely clear.
"Importantly, the ability to define patients that express certain types of molecules on their tumor surfaces will serve as an initial step toward improving treatment management and individualizing medical care," Bradbury says.
That targeting, the researchers note in the study, could include the definition of 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.
"I'm really excited about this platform," Bradbury told MDD, her words actually understating her enthusiasm in describing the large potential for use of C dots in cancer treatment.
The research will be published in the January issue of Nano Letters.
Imaging experiments in mice conducted at MSKCC showed 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 evaluate various biological properties of the tumor.
The key, Bradbury says, is the combination of porous outer shell and inner core offering "a Lego-type modular construction" that can do "a variety of things" and have "multiple-modality capabilities."
Additionally, she says that the C dots can be used in both optical and PET imaging and can be tailored to any particle size without adversely impacting their fluorescent properties.
The 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 also were able to increase their brightness by 300%, enabling cancer cells to be tracked for longer periods of time in the body.
Their inner "core" is encapsulated in a shell of silica, a non-toxic 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.
The 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, Q dots, though offering excellent brightness and good contrast, their clinical potential is limited by their large size and risk of toxicity, such as by "getting stuck in the liver," Bradbury says.
The initial clinical application identified for the new imaging agent is "to look at nodal spread of disease, head and neck tumors. A lot of surgeons like the optical capability of nanoparticles in general, for use in OR or use in the office. You could just inject the patient and use a hand-held device and shoot infrared light at the area of interest, to see if these are metastatic nodes or benign nodes."
The large benefit, she notes – and one being pursued by many others in the imaging sector is the avoidance of biopsy and repeat biopsies (see "Mauna Kea/Cellvizio push R&D microscopy/endoscopy link," Medical Device Daily, Dec. 23, 2008) – very frequently required in head and neck cancers and move directly to treatment.
She says that now that the C dot technology has been demonstrated, the next step will be to "engineer the particle platform and know all the factors, to figure out how to achieve what we want to achieve," which is "to tweak the particle to get it to do what you want it to do" for particular applications.
Additionally, that the work is moving on from concept proof to the necessary regulatory pathways. "We are sitting down after the new year, to start this, to get an IND [investigational new drug designation], this is really, really important in parallel with other studies."
Once the "fundamental platform" wins approval, she says, succeeding products can be modified and further approvals sought.