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

AMYPAD Consortium, Fiona Heeman, Maqsood Yaqub, Isadora Lopes Alves, Kerstin Heurling, Johannes Berkhof, Juan Domingo Gispert, Santiago Bullich, Christopher Foley, Adriaan A Lammertsma

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)32
JournalEJNMMI Research
Volume9
Issue number1
DOIs
Publication statusPublished - 27 Mar 2019

Cite this

AMYPAD Consortium ; Heeman, Fiona ; Yaqub, Maqsood ; Lopes Alves, Isadora ; Heurling, Kerstin ; Berkhof, Johannes ; Gispert, Juan Domingo ; Bullich, Santiago ; Foley, Christopher ; Lammertsma, Adriaan A. / Optimized dual-time-window protocols for quantitative [18F]flutemetamol and [18F]florbetaben PET studies. In: EJNMMI Research. 2019 ; Vol. 9, No. 1. pp. 32.
@article{8642b17df9a94e0a800dfa70e9bcd195,
title = "Optimized dual-time-window protocols for quantitative [18F]flutemetamol and [18F]florbetaben PET studies",
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.",
author = "{AMYPAD Consortium} and Fiona Heeman and Maqsood Yaqub and {Lopes Alves}, Isadora and Kerstin Heurling and Johannes Berkhof and Gispert, {Juan Domingo} and Santiago Bullich and Christopher Foley and Lammertsma, {Adriaan A}",
year = "2019",
month = "3",
day = "27",
doi = "10.1186/s13550-019-0499-4",
language = "English",
volume = "9",
pages = "32",
journal = "EJNMMI Research",
issn = "2191-219X",
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Optimized dual-time-window protocols for quantitative [18F]flutemetamol and [18F]florbetaben PET studies. / AMYPAD Consortium ; Heeman, Fiona; Yaqub, Maqsood; Lopes Alves, Isadora; Heurling, Kerstin; Berkhof, Johannes; Gispert, Juan Domingo; Bullich, Santiago; Foley, Christopher; Lammertsma, Adriaan A.

In: EJNMMI Research, Vol. 9, No. 1, 27.03.2019, p. 32.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Optimized dual-time-window protocols for quantitative [18F]flutemetamol and [18F]florbetaben PET studies

AU - AMYPAD Consortium

AU - Heeman, Fiona

AU - Yaqub, Maqsood

AU - Lopes Alves, Isadora

AU - Heurling, Kerstin

AU - Berkhof, Johannes

AU - Gispert, Juan Domingo

AU - Bullich, Santiago

AU - Foley, Christopher

AU - Lammertsma, Adriaan A

PY - 2019/3/27

Y1 - 2019/3/27

N2 - 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.

AB - 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.

U2 - 10.1186/s13550-019-0499-4

DO - 10.1186/s13550-019-0499-4

M3 - Article

VL - 9

SP - 32

JO - EJNMMI Research

JF - EJNMMI Research

SN - 2191-219X

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ER -