Theranostics could translate personalized medicine from research to reality by harnessing molecular imaging to target drug delivery to specific cellular features characteristic of an individual patient’s disease. However, the nature of individualized medicine also may be the Achilles' heel for theranostics.
The potential for a pharmaceutical blockbuster is next to nil because each treatment will target a select group of patients.
As some researchers explore the clinical potential in areas from prostate cancer to diabetes, others are troubleshooting regulatory and economic hurdles.
Theranostics is complex, but various parts of all necessary, components are working in the research setting, says Daniel Y. Lee, MD, PhD, director of the PET Center at The Methodist Hospital Research Institute in Houston. However, the entire system required to translate theranostics to clinical practice is not yet working together.
As the pace of research accelerates, researchers need to prepare for other challenges. In fact, regulatory issues, rather than scientific challenges, present the primary barrier to catalyzing theranostic drug platforms, says Lee.
|Theranostics in Action|
|A single-entity theranostic system combines initial staging with an imaging version of specific probe (green sunburst), followed by therapy with the therapeutic version of the probe (red lightning bolt). Restaging exams are performed with the imaging probe. Patients with positive imaging results (red lesion) can be treated with the therapeutic agent. Patients with negative results will not be treated with the agent.|
|© 2011 by American Roentgen Ray Society / Lee D Y , Li K C P AJR 2011;197:318-324|
Theranostics is best exemplified by the use of radioactive iodine to image and treat thyroid diseases. This dual function is possible because of the characteristics of the radioactive element and the natural mechanism of concentrating iodine by thyroid cells. When this biochemical mechanism is lost as in certain forms of aggressive thyroid cancers, then radioiodine therapy is no longer effective, underscoring the need for active targeting. Modern theranostics promises to target treatment to the appropriate tissue.
One-half of the theranostics equation is the new class of drugs based on molecular targeting. These drugs are designed to take action on a specific receptor or other gene product characteristic of the disease. For example, women with breast cancer are tested to assess the status of human epidermal growth factor receptor 2 (HER2). Women with positive results are candidates for trastuzumab (Herceptin, Genentech) therapy, a biological drug that specifically targets HER2.
Molecular imaging can be leveraged to combine noninvasive imaging and targeted drug delivery. Imaging agents are typically small molecules or biologics with tumor-seeking properties. Combining these imaging agents with disease-destroying payloads, such as radioisotopes or drugs, can produce customized theranostics.
Nanometer-sized materials are the newest additions to this platform. The composition and size of these nanomedicines allow for multiple components to be carried. By choosing the right combination of targeting, imaging and therapeutic payloads these nanomedicines provide opportunities for drug development. “We are on the cusp of creating new nanoparticle-based, multipurpose targeting vehicles,” confirms Lee.
Using the analogy of a car model, the nanoparticle serves as the platform for theranostics, but it can be accessorized differently depending on the patient’s specific disease. Some nanoparticles require GPS for guidance; others require a larger trunk with remote control operation; and still others require sophisticated communication tools, such as headlights that flash to indicate a car’s location.
Imaging with a theranostic agent can visualize receptors or proteins in a disease process and determine if a patient is responding to therapy.
Although the last two decades have brought progress in nanomedicine, significant challenges remain.
While researchers have made progress in the development of nanoparticles, the capability to activate drug delivery has lagged behind. “We need to control the trigger, so that the drug is delivered to the appropriate target. The challenge is finding the right combination of targeting agents, vehicles and control elements to make the trigger work,” says Lee. “These are solvable problems.”
In the research lab
Zaver Bhujwalla, PhD, director