Comparison of methods for evaluating aromatase (AR) in the human brain with PET and [N-methyl-11C]vorozole ([11C]VOR)

Objectives The final step in the biosynthesis of estrogen is catalyzed by AR. [11C]VOR is a tracer for AR. Although [11C]VOR uptake in regions of high AR concentration increases over time, it is well described by a reversible 2 compartment (2C)model. We seek the optimum method of evaluating the total distribution volume (VT).

Methods The brain distribution of [11C]VOR was measured in 40 baseline studies (27 normal subjects). Average injected dose was 5.51 ± 1.3mCi. PET scans lasted 90 min (Siemen’s HR+). An arterial plasma input function was obtained and the fraction of unchanged [11C]VOR was determined. Region of interest (ROI)data were analyzed using a 2C 4 parameter model (K1, k2, k3 and k4) to calculate VT. For comparison VT estimates were determined by fixing k4 at a value from an average ROI of the 4 highest regions (hypothalamus HYP, thalamus THL, amygdala and preoptic area) for each subject. Using this k4 VT for the individual regions were determined. Also VT was estimated by graphical analysis (GA) and by the tissue to plasma ratio (TR) from 60 to 90min.

Results HYP average VT estimates were 5.27 ± 1.5, 5.4 ± 1.6, 4.2 ± 1.5 and 5.16±1.5 for fix k4, vary k4, GA and TR. THL results were 4.62±1.1, 4.6±1.1, 4.0 ± 1.0 and 4.3 ± 1.0. The average over subjects of VT ratio for HYP/THL was 1.17±.18 (fix k4) compared to 1.16 ± .28 (vary k4). The lowest uptake is in cerebellum with VT estimates (as above) 1.67±.32, 1.54±.32, 1.44 ±.3, 2.24±.5.

Conclusions Because the variability in HYP/THL ratio is decreased by fixing k4,individual estimates are less sensitive to noise. However the k4 for the high binding regions is not appropriate for the low regions. TR for the high regions agrees well with the 2C VT estimates but overestimates VT for the low regions. GA gives VT estimates that agree well with 2C for the low regions. The implication for generating parametric images is that a combination of methods may be necessary depending upon regional tracer uptake.

Research Support DOE/OBER infrastructure and BNL