Reference Tissue Models and Blood-Brain Barrier Disruption: Lessons from (R)-[11C]PK11195 in Traumatic Brain Injury

Abstract

(R)-[¹¹C]PK11195 is a tracer for activated microglia. The purpose of this study was to assess the validity of the simplified reference tissue model for analyzing (R)-[¹¹C]PK11195 studies in traumatic brain injury (TBI), where blood–brain barrier disruptions are likely. Methods: Dynamic (R)-[¹¹C]PK11195 scans were acquired at 3 time points after TBI. Plasma input–derived binding potential (BP_ND^PI), volume of distribution (V_T) and K₁/k₂, and simplified reference tissue model–derived binding potential (BP_ND^SRTM) were obtained. Simulations were performed to assess the effect of varying K₁/k₂. Results: Early after TBI, an increase in V_T, but not in BP_ND^PI, was found. Early K₁/k₂ correlated with V_T and BP_ND^SRTM but not with BP_ND^PI. One and 6 mo after TBI, BP_ND^SRTM correlated with BP_ND^PI. Conclusion: Early after TBI, (R)-[¹¹C]PK11195 studies should be analyzed using plasma input models.