19F-Magnetic Resonance Spectroscopy to evaluate antidepressant exposure & patient-level factors affecting adolescent brain disposition

Motivation: Medication response in adolescent depression is unpredictable and relationships between dose, brain concentrations and clinical response are unknown. Goal(s): 19F-MRS is uniquely suited to study pediatric brain disposition, as it’s non-invasive, non-radiolabeled and less than minimal risk. Approach: Youth (n=52) aged 12-21 taking fluoxetine completed 19F-MRS at 3T. Results: Brain fluoxetine concentrations exceeded plasma concentrations by 9 to 304-fold. Dose-normalized brain concentrations varied 13-fold, explained by plasma concentration and dose with small contributions from BMI, CYP2D6 and ABCB1. 19F-MRS is a valuable tool for studying pediatric brain disposition of fluorine-containing medications and enables inquiry into patient factors that impact brain exposure and response. Impact: In vivo 19F-MRS measures brain concentrations of fluorine-containing medications and enables inquiry into individual-level factors contributing to brain disposition. This approach fills a critical gap in pediatric drug development, especially where other imaging modalities (e.g., PET) are not feasible.