, , ,

Brian MoyerBrian Moyer is president and principal of BRMoyer & Associates and a full-time senior science advisor for the Biomedical Advanced Research and Development Authority (BARDA), of the Assistant Secretary for Preparedness and Response (ASPR). Connect with Brian on LinkedIn at http://www.linkedin.com/pub/brian-r-moyer/3/b19/495.

From time to time in my pharmacology studies, I have found a need to visualize where my drug is in the body and what is going on pharmacodynamically, e.g., a need to measure a physiological function, or a need to examine response time of a drug-receptor interaction. I have found the view of the pathologist, i.e., histology, to be the “gold standard,” certainly. But histology takes time, takes expertise, and typically one loses the ability to measure a specific phenomenon in the same animal over time. Today I can do exactly that with a wide variety of imaging platforms. Advances in imaging sciences have provided many new tools to do the above activities and to do so in a quantitative manner. Imaging sciences have become a major new tool in the armament of the drug/biologic scientist.

Watching cells move through the vasculature and witnessing the tumble and the cell-vascular wall interaction can be done using confocal microscopy. Measurements of the time for a cell to traverse a vascular bed relative to a drug concentration is one of the newest tools in real-time imaging. Another is BOLD (blood oxygen level dependent) imaging using MRI, where we can actually see positional information on brain blood flow localized within millimeters, and in real time, where a person’s response to questions or stimuli can be assessed. We can “see” where your brain is “thinking.”

Pharmaco-imagingIn another brain research area, investigators of Alzheimer disease (AD) now have additional probes to investigate the extent of involvement of amyloid plaque buildup that dissociates the nerve tracts in the brain destroying cognitive processing. There are now four imaging contrast agents for positron emission tomography where brain “breadslices” can be reconstructed giving an almost “histologic” analysis of the living brain, with a time component, in terms of the changing maps of glucose metabolism using F-18 deoxyglucose, maps of blood flow using Rb-82, amyloid deposition maps using C-11 PIB, and a new F-18 tracer for amyloid, F-18 Florbetapir. The ability to measure the amyloid along with blood flow and sugar metabolism together–and especially in a “living histologic” region-by-region way–now provides a path to measure efficacy of new AD therapies. These agents coupled with CT (computed x-ray tomography), MRI, or ultrasound, each for anatomical overlay and image construction corrections, provide investigators with “function/distribution images” that can quantify, in real-time, drug or biologic effects, which can help make rapid and accurate clinical decisions and improve medical care.

The new book Pharmaco-Imaging in Drug and Biologics Development: Fundamentals and Applications was edited and authored by myself along with Narayan Cheruvu, Ph.D, and Tom C-C. Hu, Ph.D. As former chairs for the AAPS Pharmaco-Imaging focus group, Narayan and I felt this book was a timely addition to the pharma/biotech toolbox. The goal was to prepare a book that moves away from “what new agents have been developed” to emphasize “how do we use the agents we have.” The enormity of the subject matter, the diversity of imaging platforms and agents, and imaging’s coverage of “all of biology” made for a challenge, but we hope the knowledge collected from this volume will be helpful to create “imaging” in your own diagnostic or therapeutic product development setting.