Hydrophilic Tzs result in the best in vitro contrast, but more lipophilic Tzs are reported to enter the brain better. To investigate this trade-off and identify a Tz that would provide an optimal combination of imaging contrast and brain uptake, we assessed the brain uptake and washout of all 18 F-Tzs in vivo by dynamic PET scans in healthy Long-Evans rats (SI Section S9). Time activity curves (TACs) for the whole brain were expressed in %ID/mL tissue. We expected that F-Tz that show high peak uptake in the brain followed by fast washout are most likely best suited for pretargeted imaging. High initial uptake increases the possibility of the Tz to bind to their targets and fast wash-out decreases background levels. Consequently, Tzs with these properties should result in a high imaging contrast. We used the peak uptake as a measure of the brain uptake and the inverse area under the curve (AUC) as a measure for the washout. The ratio between uptake and washout (peak/AUC) was used to rank 18 F-Tzs (Figure ). This value describes best the interplay between high initial uptake and fast washout. As higher it is, as better the interplay. Interestingly, peak/AUC ratios strongly correlated with clogP and clogD7.4 within the same Tz motif (SI Figure ). The most lipophilic Tzs from each class (2, 10, 14 and 18) displayed the best peak/AUC ratios.