Evaluation of Tracer Kinetic Models for Analysis of [F-18]FDDNP Studies

Different pharmacokinetic methods for [F-18]FDDNP studies were evaluated using both simulations and clinical data. 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, BPND, was obtained both directly (=k (3)/k (4)) and indirectly (using volume of distribution ratios). For clinical data, 2T1M was preferred over 2T4k according to Akaike criterion. Indirect BPND using 2T1M correlated better with SRTM then direct BPND. Fairly constant volume of distribution of metabolites was found across brain and across subjects, which was strongly related to bias in BPND obtained from SRTM as seen in simulations. Furthermore, in simulations, SRTM showed constant bias with best precision if metabolites entered brain. SRTM is the method of choice for quantitative analysis of [F-18]FDDNP even if it is unclear whether labeled metabolites enter the brain.