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

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  • dc.contributor.author Heeman, Fiona
  • dc.contributor.author Yaqub, Maqsood
  • dc.contributor.author Lopes Alves, Isadora
  • dc.contributor.author Heurling, Kerstin
  • dc.contributor.author Berkhof, Johannes
  • dc.contributor.author Gispert López, Juan Domingo
  • dc.contributor.author Bullich, Santiago
  • dc.contributor.author Foley, Christopher
  • dc.contributor.author Lammertsma, Adriaan A.
  • dc.contributor.author AMYPAD Consortium
  • dc.date.accessioned 2020-07-22T06:39:08Z
  • dc.date.available 2020-07-22T06:39:08Z
  • dc.date.issued 2019
  • dc.description.abstract 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.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation 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
  • dc.identifier.doi http://dx.doi.org/10.1186/s13550-019-0499-4
  • dc.identifier.issn 2191-219X
  • dc.identifier.uri http://hdl.handle.net/10230/45152
  • dc.language.iso eng
  • dc.publisher Springer
  • dc.relation.ispartof EJNMMI Res. 2019; 9(1):32
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/115952
  • dc.rights © 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.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Alzheimer’s disease
  • dc.subject.keyword Amyloid
  • dc.subject.keyword Florbetaben PET
  • dc.subject.keyword Flutemetamol PET
  • dc.subject.keyword Quantification
  • dc.subject.keyword Simplified methods
  • dc.title Optimized dual-time-window protocols for quantitative [18F]flutemetamol and [18F]florbetaben PET studies
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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