ALUMNUS DUSTIN WOOTEN: Direct and rapid impact

Bill Bell
for Illinois Physics

Before a pharmaceutical company can heal people and make their lives better, before it can market its next blockbuster medicine, before it can run a clinical trial, before it even identifies a way of attacking an illness or develops a drug in the first place—there’s basic science to be done. The company has to know how those medicines will interact with the body and see what’s going on at the chemical level. And that involves some serious physics.

That’s where Dustin Wooten comes in. Wooten earned a bachelor’s degree from Illinois Physics in 2008. He is now principal research scientist and head of image analysis within the Translational Imaging Group at AbbVie, the 50,000-person, $250 billion-firm based in northern Illinois, which spun off from Abbott Laboratories about a decade ago.

“To me, one of the draws of the medical field is having more of a direct and rapid impact on people’s lives.”

Wooten’s team takes images generated by non-invasive imaging techniques like PET scans or MRIs and derives quantifiable data that can be used in clinical trials and other studies. In other words, they write the code and establish the image-processing steps used to assess a few to thousands of scans consistently, allowing researchers to determine how and how well potential therapies are working.

It’s a tricky business. Molecules that are drug candidates or that can measure physiological effects of drug candidates are labeled with radioactive atoms like Fluorine-18, which decay rapidly by emitting low-energy positrons. The radioisotopes that result can be imaged by a PET scanner but, importantly, they remain physiologically identical to their non-radioactive equivalent. The positrons that they emit collide with electrons in other molecules, releasing a pair of gamma photons.

Wooten explains, “The PET scanner detects these gamma rays, and because we know they are traveling in opposite directions along a straight line, we know the positron emission had to happen somewhere along that straight line. This gives us the spatial information we need about where the radioactive molecule was located. By combining all this data and making some corrections, we can generate a 3D—or even 4D, including time—distribution of the radioactive molecules in the subject.”

Expert image analysis by Wooten’s team allows researchers to determine characteristics like where a therapeutic drug travels, how quickly it moves through the body, how long it lasts, or even pharmacodynamics.

Imagine the sort of selective serotonin reuptake inhibitors (SSRIs) that are often used to treat depression. They are taken orally, absorbed by the body, carried to the brain, bind to the proteins that carry messages among nerve cells, and are finally flushed from the body. PET scan imaging and image analysis could be used to track parts of that process and identify which candidate drugs most effectively bind to the proteins and are effective for the longest period of time. Those insights allow researchers to pick the most promising candidates and develop the most appropriate clinical trials to test them.

The technique can be applied to both the candidate therapeutics being tested and their targets—in our example, either the SSRI or the neurotransmitter protein.

“Say we have a receptor that is abundant in the brain, and we’ve developed a therapeutic that targets that receptor,” says Wooten. “It would be great if we could show that our therapeutic is engaging that receptor. There are potentially in vitro methods of detecting this, but it’s always more reassuring to know target engagement is happening in vivo. Thus, if we have a PET radiotracer that engages that same receptor, we, in theory, have our solution, which would involve several PET scanning sessions.

“In the first scan, we inject only radiotracer, and we see high uptake in the brain. In the second scan, we inject a small dose of the therapeutic prior to the radiotracer injection and PET imaging, and we see less radiotracer uptake. In the last scan, we inject a large amount of the therapeutic prior to the radiotracer injection and PET imaging, and this time we see little to no uptake of the radiotracer in the brain. This demonstrates target engagement because the therapeutic is reducing the number of available receptors for the radiotracer to bind to.”

Ultimately, these types of studies can help determine which candidates are most promising, as well as other factors like what doses of the candidates should be used in clinical trials.

Wooten worked in PET imaging long before joining AbbVie, first as a doctoral student at the University of Wisconsin. He had considered medical school but stumbled on medical physics and imaging while an undergrad at Illinois.

“In my research on various medical schools, I came across the field of medical physics, and it piqued my interest—this would allow me to remain grounded in physics,” Wooten recalls. “I honestly didn’t know the field existed before coming across it in an online search. It came up in Google’s search suggestion after typing ‘medical’. UW-Madison had pioneered one of the most prestigious medical physics programs in the country and was right next door.”

After earning his doctoral degree, Wooten continued his training in Boston. He served as a postdoc and faculty member at Harvard Medical School (HMS) and Massachusetts General Hospital (MGH). His work was focused on medical imaging in research, while he also spent time in the clinic and teaching.

A growing family brought Wooten back home to Illinois. (Family is obviously important to Wooten. We conducted our interview in two parts, just before and just after a vacation to Table Rock Lake, Missouri, with his wife and three sons. No interruptions while on the lake!)

“My wife and I had been in Boston for 4 years,” says Wooten. “My wife was a speech and language pathologist at a local nonprofit hospital. I was junior faculty at MGH and HMS, conducting research, performing clinic work, and teaching. We both loved our careers, positions, mentors, colleagues, and the Boston area.

“However, around this time, we found out we were adding our first addition to our family. We were very excited about this, but the thought of expanding our new family while being so far from our own families seemed a bit daunting.”

AbbVie offered many of the same charms as academic life and a home base back in Illinois. For Wooten, it’s been a great fit—and an opportunity to do good.

Wooten reflects, “To me, one of the draws of the medical field is having more of a direct and rapid impact on people’s lives.”