Fancy Cameras and Designing Better Drugs

Setting: The Imaging Sciences Pathway Retreat, hosted by Washington University WUSTL at the beautifully historic downtown St. Louis Union Station. Topic of Conversation: Improving drug discovery and development through medical imaging technologies, technologies that use fancy cameras to visualize the inner workings of the human body.

This is the third blog post in a series covering a WashU conference on groundbreaking technologies and discovery pathways in medical imaging. Medical imaging involves taking images of the human body and internal organs, tissues, and cells for the purposes of diagnosis and treatment of disease. More recently, medical imaging may also facilitate new drug discovery and development from pre-clinical trials to FDA(1) approval. Dr. J. L. Evelhoch from Merck Research Laboratories opened the ISP retreat with a discussion on exactly how fancy cameras that can ‘see’ through a human skull and spot a lurking tumor can also help researchers design and produce better drugs for the treatment of diseases such as cancer.

Designing and developing a new drug is no easy task. The process requires many steps and a long process of various animal and human trials. An extensive amount of pre-discovery ‘tweaking’ of various drug compounds and years of clinical trials may lead to only one FDA approved drug, if the drug ever enters the FDA review step at all. Most potential drugs fail for either of two primary reasons: insufficient efficacy (insufficient ability of the drug to produce a beneficial change or therapeutic effect) or insufficient safety for human use. Failure rates in today’s drug development industry are also disheartening: a half of all potential drugs fail in the transition between phases 1 and 2 clinical trials, and two-thirds of all drugs fail in the transition between phases 2 and 3. Because the costs for phase 2 and phase 3 clinical trials are substantial, failures of potential drugs once they reach these stages mean a lot of time and money wasted, and a return ‘back to ground zero’ with pre-discovery drug studies. In other words, current trends in the drug industry are seeing the US “spend more money, while not getting as many products,” – Dr. Evelhoch.

A question that arises for medical researchers and drug companies is, how can we better identify winners and losers from the pool of potential drug compounds? A common answer to this question in today’s scientific community is multifaceted: (1) biomarkers for safety, and (2) the use of imaging technologies.

Biomarkers are traceable molecular indicators of, for example, a patient’s response to therapy with a new drug. Biomarkers can “provide critical information on effects of drug treatment,” says Dr. Evelhoch. They can be used to tell whether a drug actually hits its target or not, and whether the drug is safe when administered throughout the human body. Biomarkers must be fit for their unique purpose, and must be tested in a similar process to actual drug testing. With the use of appropriate biomarkers, researchers may significantly reduce the time and failure rate of new drugs in pre- and clinical trials.

“Imaging as a Biomarker.”

When we speak of ‘traceable’ biomarkers, we may talk about medical imaging as the means by which we ‘trace’ or follow these biomarkers inside the human body. While drug discovery is traditionally costly and inefficient, integrating biomarkers and medical imaging can make this process much better, according to Dr. Evelhoch. Indeed, researchers today are challenged to ’integrate quantitative imaging into clinical practice," says Evelhoch. For example, a form of X-ray imaging, called DXA (Dual-emission X-ray absorptiometry), can be used to measure bone strength and to assess whether or not drugs designed to reduce bone desorption (the breakdown of bone) are working in osteoporosis patients. In this case, DXA imaging is being used as the biomarker, an indicator of whether or not the drug treatment is effective.

Imaging the Alzheimer’s Brain:

Another example of using imaging and biomarkers to improve drug discovery and development lies in the early diagnosis and potential treatment of Alzheimer’s disease. It has been hypothesized that changes in levels of beta-amyloid, the peptide that forms the brain plaques primarily implicated in causing the symptoms of this disease, occur decades before clinical symptoms of memory loss or dementia.

While several drugs have been tested for the treatment of Alzheimer’s, drug trials are typically performed in patients already demonstrating symptoms of the disease. These patient’s brains have most likely undergone irreversible changes in beta-amyloid peptide levels and plaque formation. Future drug trials aim to take place much earlier, with the use of radioactively traceable biomarkers and nuclear imaging. Beta-amyloid peptide compounds tagged with radioactive labels may be followed inside the brain with specialized cameras that are sensitive to the radioactivity being emitted by the markers. Such biomarker imaging can help to determine early on whether an individual will progress in the disease, and whether or not new drugs can prevent its onset.

The key messages in Dr. Evelhoch’s talk at the ISP retreat were as follows: drug discovery is costly and inefficient, but medical imaging can help. What is left if to convince the FDA and medical insurance companies that imaging assays are “reasonable, necessary, and add value to patient outcome,” says Dr. Evelhoch. There is no doubt that biomarker and imaging technologies have an incredible potential to help our struggling drug discovery and development market.


(1) U.S. Food and Drug Administration


(1) Phases of clinical trial. Created by Paige Brown, Data from Wiki Commons & Dr. Evelhoch, "Merck ":

(2) YouTube video, DEXA – Dual Energy X-Ray Absorptiometry

(3) Beta-Amyloid Plaques, Wiki Commons Image

Vallabhajosula S (2011). Positron emission tomography radiopharmaceuticals for imaging brain Beta-amyloid. Seminars in nuclear medicine, 41 (4), 283-99 PMID: 21624562

Elisabeth G.E. de Vries, Thijs H. Oude Munnink, Marcel A.T.M. van Vugt and Wouter B. Nagengast (2011). Toward Molecular Imaging-Driven Drug Development in Oncology Cancer Discovery : 10.1158/2159-8274