PET tracer could aid in prevention of epilepsy drug resistance

An estimated 30 percent of epileptics experience drug resistance. A PET agent may one day be used to track physiological mechanisms of resistance, according to a study published online Oct. 3 in the Journal of Nuclear Medicine.

Andrey Postnov, from the departments of radiology and nuclear medicine, VU University Medical Center, Amsterdam, The Netherlands, and colleagues tested the safety and dosimetry of C-11 laniquidar as a biomarker for overexpression of multidrug transporters in the brain that disrupt drugs’ access to the central nervous system. Previous studies have shown that such transporters, especially the P-glycoprotein (P-gp), are overexpressed at the blood brain barrier, an important discovery on the road to understanding why so many epileptics’ drug treatments fail.

“It has been proposed that changes in P-gp expression or function at the blood–brain barrier play an important role in pharmacoresistance in epilepsy,” wrote Postnov et al. “The multidrug transporter P-gp and other efflux transporters actively transport substrates, including many central nervous system drugs, against a concentration gradient from brain to blood and cerebrospinal fluid. Hence, overexpression or increased activity of the transporter system may result in reduced tissue concentrations of central nervous system drugs in the brain, thereby greatly limiting their therapeutic efficacy.”

For this study, a sequence of 10 whole-body PET scans were performed on six healthy subjects within a 70-minute period. A blood analysis was also conducted. Results of imaging showed substantial uptake of C-11 laniquidar in the lung, kidneys, spleen and most significantly in the liver. In contrast, uptake in the brain was relatively low. Biodistribution for this tracer set the optimal dose at about 3.69 mSv for men and 4.76 mSv for women. C-11 laniquidar was found to be safe and total dose was gauged at about 2 mSv for a neuro PET/CT scan.

As an interesting point of departure, this tracer has different kinetics depending on the species of subject. The highest uptake in a single organ in rat models was the lung, whereas in human subjects it was the liver. 

“It is not known why lung uptake seems to be species-dependent,” wrote the authors.