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Optimized dual-time-window protocols for quantitative [18F]flutemetamol and [18F]florbetaben PET studies Heeman, Fiona Yaqub, Maqsood Lopes Alves, Isadora Heurling, Kerstin Berkhof, Johannes Gispert, Juan Domingo Bullich, Santiago Foley, Christopher Lammertsma, Adriaan A. AMYPAD Consortium Alzheimer’s disease Amyloid Florbetaben PET Flutemetamol PET Quantification Simplified methods 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 [18F]flutemetamol and [18F]florbetaben studies. Methods: Rate constants for subjects across the Alzheimer's disease spectrum (i.e., non-displaceable binding potential (BPND) in the range 0.02-0.77 and 0.02-1.04 for [18F]flutemetamol and [18F]florbetaben, respectively) were established based on clinical [18F]flutemetamol (N = 6) and [18F]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 BPND, outliers (≥ 1.5 × BPND max) were removed and the bias was assessed using the distribution volume ratio (DVR = BPND + 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: [18F]Flutemetamol and [18F]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 [18F]flutemetamol and [18F]florbetaben, respectively). Conclusions: The length of the interval inversely correlates with the accuracy of the BPND estimates. Consequently, a dual-time-window protocol of 0-30 and 90-110 min (=maximum of 60 min interval) allows for accurate estimation of BPND values for both tracers. [18F]flutemetamol: EudraCT 2007-000784-19, registered 8 February 2007, [18F]florbetaben: EudraCT 2006-003882-15, registered 2006. 2020-07-22T06:39:08Z 2020-07-22T06:39:08Z 2019 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Heeman F, Yaqub M, Lopes Alves I, Heurling K, Berkhof J, Gispert JD, Bullich S, Foley C, Lammertsma AA; AMYPAD Consortium. Optimized dual-time-window protocols for quantitative [18F]flutemetamol and [18F]florbetaben PET studies. EJNMMI Res. 2019; 9(1):32. DOI: 10.1186/s13550-019-0499-4 2191-219X http://hdl.handle.net/10230/45152 http://dx.doi.org/10.1186/s13550-019-0499-4 eng EJNMMI Res. 2019; 9(1):32 info:eu-repo/grantAgreement/EC/H2020/115952 © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf application/pdf Springer