AJR: A molecular theranostics primer
Molecular theranostics holds promise, offered a review published in the August issue of American Journal of Roentgenology.
The article detailed methods and hurdles to the clinical implementation of molecular theranostics. Theranostics uses a diagnostic test to determine whether a patient may benefit from a specific therapy, explained Daniel Y. Lee, MD, and King C. P. Li, MD, of the department of radiology, nuclear medicine division at the Methodist Hospital Research Institute in Houston. Lee and Li pointed to an immunohistochemical test to determine HER2 expression as a prerequisite to Herceptin treatment as an example. Molecular theranostics, they continued, integrates a diagnostic test with a therapeutic intervention targeting a molecular feature of disease.
“The main reason for the tremendous excitement of theranostics is its revolutionary approach that promises improved therapy selection on the basis of specific molecular features of disease, greater predictive power for adverse effects and new ways to objectively monitor therapy response. These properties are fundamental elements of personalized medicine,” Lee and Li wrote.
One of the newest avenues is nanomedicines, nanoparticle-based therapeutics composed of organic and inorganic materials, which offer multiple advantages. These include: the ability to carry targeting agents, imaging moieties and drugs in configurations not readily possible with conventional small organic molecules. In addition, they may reinvigorate drug candidates shelved because of solubility or pharmokinetic issues.
Lee and Li divided theranostic nanomedicines into untargeted and targeted agents, with current agents falling into the untargeted category. These agents accumulate at tumor sites through variably leaky vasculature, they explained. The addition of chemical or biological ligands can enable targeting.
An imaging probe can be converted into a single-entity theranostic agent, continued Lee and Li, by modifying the radionuclide from a y-emitter (111In) to a B-emitter (90Y). “If the diagnostic scan is positive for the presence of the target (e.g., cellular receptor), the patient can be treated with the therapeutic agent to detect the presence or absence of diseased tissue.”
The advantage of the approach is the ability to determine specific pharmokinetic parameters and biodistribution via imaging results, noted the authors.
Despite the promise of molecular theranostics, significant barriers remain. Cost, which stretches to $200 million to introduce a diagnostic imaging agent and more than $800 million for a therapeutic drug, tops the list, partially because the payoff for theranostics may not provide the same level of return as blockbuster drugs.
However, “phase 0” FDA trials, also known as microdosing trials, could trim the cost of bringing radionuclide theranostics to market. Lee and Li emphasized, “However the very strength of molecular theranostics will also ironically limit the pool of potential patients who may benefit from any specific agent. Clearly, for this approach to take foothold, the cost of drug development must be significantly reduced.”
The authors also identified the potential need for further specialization within diagnostic radiology and possible development of a new subspecialty of medicine, and concluded, “the landscape of medicine will likely change because future theranosticians will inevitably share or fully adopt the care of patients with disease that will be molecularly characterized, a requisite step toward individualized medicine.”