Brian Moyer is currently contracted to the Biomedical Advanced Research and Development Authority, Health and Human Services, Washington, D.C., as senior science advisor, Project BioShield, Chemical, Radiologic and Nuclear Threats, through Tunnell Government Services, Bethesda, Md.
“Modern medicine” has morphed into “molecular medicine,” and it has taken on this new identity in part due to the capabilities of imaging. Imaging used to mean the view through the microscope, but advances over the years in photomultiplier tubes and collimation led to nuclear medicine imaging in the 1950s, and computational techniques with data storage and advances in electronic miniaturization led to new clinically important 3-D imaging systems in the latter half of the past century. In the 21st century we now have the capability of viewing biology using an extraordinary variety of imaging platforms that can contribute dramatically to our understanding of drug and biologics mechanisms of action as well as their toxicities. Modern imaging platforms have revolutionized how we can “see” pharmacology—pharmacology is now “visible.”
Medical imaging contributed significantly in the discovery of molecular biomarkers, and these advances drove the development of imaging platforms. In the 1990s, applications of polymerase chain reaction in gene mapping and protein expressions defining pathologies led to many new ideas on how to track and follow disease using imaging. The creation of this expanding “biomarker” library has allowed imaging scientists to help define diseases not through the microscope but through the visualization of a pathology’s pharmacodynamics, i.e., tracking and localizing patho-specific biomarkers or cells. The recent additions of optical imaging with quantum dots, libraries of knockout/in mice, analytical methods applied to imaging MALDI and NIMS, and MRS imaging have made small, regional sampling possible. The drug development paradigm is now shifting from the formalism of the pharmacology and toxicology paths of the last century that has served us well to a potentially revolutionary path, which will reduce animal usage and obtain time rate of change of biomarker and physiologic responses to drugs and interventional strategies.
Wang and Deng have written a very concise review on medical imaging in drug development. Bocan also provided a good overview of the advances in imaging platforms. A review I published in 2009 covers the advantages and caveats of biomarker imaging through the chemistry and physics employed by several platforms. Knock-in/out mouse models are also aiding drug investigations using imaging. Cell therapies are fast becoming a topic of novel drug delivery as well as defining cell trafficking in disease as well as under various treatment paradigms. Bioluminescent and positron tomography (PET) techniques are fast becoming applicable in the nonclinical setting for cell tracking and will be utilized clinically in the near future.
As an example of how imaging and biomarkers have contributed to new advances, one simply can look at Alzheimer’s disease (AD). AD was described in the 1800s through examination of post-mortem brain tissues for deposits of beta-amyloid. Today we can view this amyloid deposition in vivo with noninvasive imaging platforms and novel molecular probes with affinity for amyloid. The search for such agents began, however, by measuring changes in glucose metabolism as a response of amyloid invasion and disruption of neuroanatomical circuitry. F-18 FDG was, and is still today, used for evaluation of the brain distributive changes of glucose metabolism. Novel amyloid-avid radiotracers have been developed first with Pittsburgh Compound-B, which is labeled with C-11, and now Lilly (through acquisition of Avid Pharmaceuticals) has a novel PET tracer, AMYViD, which was FDA approved in 2012 for imaging specifically beta-amyloid neuritic plaques. As we can now measure the deposition of amyloid in a patient, we may potentially apply this agent to drug development of agents that can attenuate or even abolish the insidious progressive deposition of beta-amyloid that eventually degrades cognitive ability. Having a noninvasive tool to assess brain amyloid as a biomarker of AD provides an opportunity to exploit novel treatment strategies and measure their effectiveness.
Molecular medicine is now the exploitation of patho-specific “biomarkers” to detect disease. Physicians can now “find, fight, and follow” disease using imaging and the need for new novel disease biomarkers is in high demand. It is an impossible task to list or discuss all the possibilities and ideas that are possible for imaging. It is imperative that regulatory acceptance of any imaging technology used in the development of a drug or biologic should always be paramount in the decision to use, develop, or engage in the use of an imaging platform. Learn more about imaging platforms at the 2013 AAPS National Biotechnology Conference hot topic session Imaging Platforms in Drug Development: Pharmacology is Now Visible.