Evaluation of tracer kinetic models for analysis of [18F]FDDNP studies.
OBJECTIVE
Different pharmacokinetic methods for [18F]FDDNP studies were evaluated using both simulations and clinical data.


METHODS
Methods included two-tissue reversible plasma (2T4k), simplified reference tissue input (SRTM), and a modified 2T4k models. The latter included an additional compartment for metabolites (2T1M). For plasma input models, binding potential, BP(ND), was obtained both directly (=k (3)/k (4)) and indirectly (using volume of distribution ratios).


RESULTS
For clinical data, 2T1M was preferred over 2T4k according to Akaike criterion. Indirect BP(ND) using 2T1M correlated better with SRTM then direct BP(ND). Fairly constant volume of distribution of metabolites was found across brain and across subjects, which was strongly related to bias in BP(ND) obtained from SRTM as seen in simulations. Furthermore, in simulations, SRTM showed constant bias with best precision if metabolites entered brain.


CONCLUSIONS
SRTM is the method of choice for quantitative analysis of [18F]FDDNP even if it is unclear whether labeled metabolites enter the brain.
Yaqub
Maqsood
M
Department of Nuclear Medicine & PET Research, VU University Medical Centre, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands. Maqsood.Yaqub@VUmc.nl
Boellaard
Ronald
R
van Berckel
Bart N M
BN
Tolboom
Nelleke
N
Luurtsema
Gert
G
Dijkstra
Anke A
AA
Lubberink
Mark
M
Windhorst
Albert D
AD
Scheltens
Philip
P
Lammertsma
Adriaan A
AA