In recent years, experimental evidence has linked brain inflammation to be a result of traumatic brain injury, even when the injury is mild (mTBI), such as concussion resulting from a sports injury. Data from animal models suggests that targeting aspects of the immune response can improve clinical outcomes post-concussion, however, additional studies are needed to fully harness the power of inflammation-based biomarkers and therapeutics in mTBI. Currently, the link between concussions, neuroinflammation, and chronic traumatic encephalopathy (CTE) are not yet fully understood, in particular, stratifying at-risk individuals most prone to secondary sequalae of mTBI. Significant research continues in this area and is led by scientists such as Kiel D. Neumann, PhD, an Assistant Professor and Director of Radiochemistry at the University of Virginia School of Medicine.
Previous studies by other researchers utilizing Positron Emission Tomography (PET), while pioneering, focus primarily on the chronic stage of neuroinflammation, long after the onset of injury. Pioneering work from Johns Hopkins has demonstrated that indeed chronic neuroinflammation persists in both retired and active athletes from the National Football League. This foundational work calls to question what happens at the acute onset of injury and what length of time is required for an athlete to functionally recover from a single concussion. In other words, Dr. Neumann and the team at the University of Virginia, hope to provide guidance for when an athlete can safely return to play. Currently, concussion evaluation and determination of “return-to-play” status is based primarily on judgement of symptoms and cognitive function. Nearly 98% of all athletes are cleared to return to play about 7-10 days after a concussion, but it is not clearly understood what levels of neuroinflammation are present at this time or beyond. In other words, while the athlete may be presenting as clinically recovered, the athlete’s brain may not be functionally recovered and the injury, compounded with additional trauma to the head, may be detrimental to allowing complete recovery.
To assess neuroinflammation, Dr. Neumann is utilizing the PET radiotracer, [18F]DPA-714. Originally developed at the University of Sydney, this radiotracer binds to the translocator-protein (TSPO) receptor. While TSPO is minimally expressed in a healthy brain, it is significantly upregulated under neuroinflammatory conditions due to focal recruitment and activation of microglia. Thus, [18F]DPA-714 PET imaging may serve as an early and sensitive indicator of neuroinflammation after concussions or head injuries.
When selecting an automated system to reliably synthesize [18F]DPA-714 patient doses, it was a “no-brainer” to choose ELIXYS. Citing the systems ease of use, Dr. Neumann stated:
“What’s great about the ELIXYS is how user friendly the platform is. Every machine you work with has its nuances, but what really sets the ELIXYS apart is how easy it is to create a sequence.”
In fact, he was able to successfully synthesize [18F]DPA-714 on the first run after translating the manual synthesis protocol into an automated ELIXYS Sequence. Shortly thereafter, the radiotracer completed qualification and validation runs and the system continues to supply doses to patients at a 0% failure rate.
Now with enrollment for the study near the halfway mark, the UVA team anticipates that there will be suggestive data to allow for a larger follow-on study. One day these results may have implications that directly impact the treatment of professional athletes and influence concussion workup in youth and collegiate athletics as well. SOFIE is ecstatic that the ELIXYS system can take part in Dr. Neumann’s groundbreaking studies and we can’t wait to see what other work we can support in the future!