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Background  A long dynamic scanning protocol may be required to accurately measure longitudinal changes in amyloid load. However, such a protocol results in a lower patient comfort and scanning efficiency compared to static scans. A compromise can be achieved by implementing dual-time-window protocols. This study aimed to optimize these protocols for quantitative [ 18 F]flutemetamol and [ 18 F]florbetaben studies.    Methods  Rate constants for subjects across the Alzheimer’s disease spectrum (i.e., non-displaceable binding potential (BP ND ) in the range 0.02–0.77 and 0.02–1.04 for [ 18 F]flutemetamol and [ 18 F]florbetaben, respectively) were established based on clinical [ 18 F]flutemetamol ( N  = 6) and [ 18 F]florbetaben ( N  = 20) data, and used to simulate tissue time-activity curves (TACs) of 110 min using a reference tissue and plasma input model. Next, noise was added ( N = 50)  and data points corresponding to different intervals were removed from the TACs, ranging from 0 (i.e., 90–90 = full-kinetic curve) to 80 (i.e., 10–90) minutes, creating a dual-time-window. Resulting TACs were fitted using the simplified reference tissue method (SRTM) to estimate the BP ND , outliers (≥ 1.5 × BP ND  max) were removed and the bias was assessed using the distribution volume ratio (DVR = BP ND  + 1). To this end, acceptability curves, which display the fraction of data below a certain bias threshold, were generated and the area under those curves were calculated.    Results  [ 18 F]Flutemetamol and [ 18 F]florbetaben data demonstrated an increased bias in amyloid estimate for larger intervals and higher noise levels. An acceptable bias (≤ 3.1%) in DVR could be obtained with all except the 10–90 and 20–90-min intervals. Furthermore, a reduced fraction of acceptable data and most outliers were present for these two largest intervals (maximum percentage outliers 48 and 32 for [ 18 F]flutemetamol and [ 18 F]florbetaben, respectively).    Conclusions  The length of the interval inversely correlates with the accuracy of the BP ND  estimates. Consequently, a dual-time-window protocol of 0–30 and 90–110 min (=maximum of 60 min interval) allows for accurate estimation of BP ND  values for both tracers.  [ 18 F]flutemetamol: EudraCT 2007-000784-19, registered 8 February 2007, [ 18 F]florbetaben: EudraCT 2006-003882-15, registered 2006.    Electronic supplementary material  The online version of this article (10.1186/s13550-019-0499-4) contains supplementary material, which is available to authorized users.

Optimized dual-time-window protocols for quantitative [18F]flutemetamol and [18F]florbetaben PET studies