Reference tissue models and blood-brain barrier disruption: lessons from (R)-[11C]PK11195 in traumatic brain injury.
(R)-[(11)C]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)-[(11)C]PK11195 studies in traumatic brain injury (TBI), where blood-brain barrier disruptions are likely.


METHODS
Dynamic (R)-[(11)C]PK11195 scans were acquired at 3 time points after TBI. Plasma input-derived binding potential (BP(ND)(PI)), volume of distribution (V(T)) and K(1)/k(2), and simplified reference tissue model-derived binding potential (BP(ND)(SRTM)) were obtained. Simulations were performed to assess the effect of varying K(1)/k(2).


RESULTS
Early after TBI, an increase in V(T), but not in BP(ND)(PI), was found. Early K(1)/k(2) 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).


CONCLUSIONS
Early after TBI, (R)-[(11)C]PK11195 studies should be analyzed using plasma input models.
Folkersma
Hedy
H
Neurosurgical Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. hedy.folkersma@vumc.nl
Boellaard
Ronald
R
Vandertop
W Peter
WP
Kloet
Reina W
RW
Lubberink
Mark
M
Lammertsma
Adriaan A
AA
van Berckel
Bart N M
BN
D000293:Adolescent; D000328:Adult; D000577:Amides / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D001930:Brain Injuries / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D049268:Positron-Emission Tomography / Q000592:standards*; D012016:Reference Values; D015203:Reproducibility of Results; D055815:Young Adult
C504060:(R)-(11C)1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide; D000577:Amides; D007546:Isoquinolines