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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2019-03-01
|
| Series: | EJNMMI Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13550-019-0499-4 |
| _version_ | 1818450901931655168 |
|---|---|
| author | Fiona Heeman Maqsood Yaqub Isadora Lopes Alves Kerstin Heurling Johannes Berkhof Juan Domingo Gispert Santiago Bullich Christopher Foley Adriaan A. Lammertsma on behalf of the AMYPAD Consortium |
| author_facet | Fiona Heeman Maqsood Yaqub Isadora Lopes Alves Kerstin Heurling Johannes Berkhof Juan Domingo Gispert Santiago Bullich Christopher Foley Adriaan A. Lammertsma on behalf of the AMYPAD Consortium |
| author_sort | Fiona Heeman |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T20:58:40Z |
| format | Article |
| id | doaj.art-171773ec862e4ee3a9f43edf0d3cedc8 |
| institution | Directory Open Access Journal |
| issn | 2191-219X |
| language | English |
| last_indexed | 2024-12-14T20:58:40Z |
| publishDate | 2019-03-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | EJNMMI Research |
| spelling | doaj.art-171773ec862e4ee3a9f43edf0d3cedc82022-12-21T22:47:38ZengSpringerOpenEJNMMI Research2191-219X2019-03-019111410.1186/s13550-019-0499-4Optimized dual-time-window protocols for quantitative [18F]flutemetamol and [18F]florbetaben PET studiesFiona Heeman0Maqsood Yaqub1Isadora Lopes Alves2Kerstin Heurling3Johannes Berkhof4Juan Domingo Gispert5Santiago Bullich6Christopher Foley7Adriaan A. Lammertsma8on behalf of the AMYPAD ConsortiumAmsterdam UMC, Vrije Universiteit Amsterdam, Radiology and Nuclear Medicine, Amsterdam NeuroscienceAmsterdam UMC, Vrije Universiteit Amsterdam, Radiology and Nuclear Medicine, Amsterdam NeuroscienceAmsterdam UMC, Vrije Universiteit Amsterdam, Radiology and Nuclear Medicine, Amsterdam NeuroscienceWallenberg Centre for Molecular and Translational Medicine and the Department of Psychiatry and Neurochemistry, University of GothenburgAmsterdam UMC, Vrije Universiteit Amsterdam, Epidemiology and BiostatisticsBarcelonaβeta Brain Research Center, Pasqual Maragall FoundationLife Molecular Imaging GmbHGE HealthcareAmsterdam UMC, Vrije Universiteit Amsterdam, Radiology and Nuclear Medicine, Amsterdam NeuroscienceAbstract 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.http://link.springer.com/article/10.1186/s13550-019-0499-4AmyloidQuantificationSimplified methodsFlutemetamol PETFlorbetaben PETAlzheimer’s disease |
| spellingShingle | Fiona Heeman Maqsood Yaqub Isadora Lopes Alves Kerstin Heurling Johannes Berkhof Juan Domingo Gispert Santiago Bullich Christopher Foley Adriaan A. Lammertsma on behalf of the AMYPAD Consortium Optimized dual-time-window protocols for quantitative [18F]flutemetamol and [18F]florbetaben PET studies EJNMMI Research Amyloid Quantification Simplified methods Flutemetamol PET Florbetaben PET Alzheimer’s disease |
| title | Optimized dual-time-window protocols for quantitative [18F]flutemetamol and [18F]florbetaben PET studies |
| title_full | Optimized dual-time-window protocols for quantitative [18F]flutemetamol and [18F]florbetaben PET studies |
| title_fullStr | Optimized dual-time-window protocols for quantitative [18F]flutemetamol and [18F]florbetaben PET studies |
| title_full_unstemmed | Optimized dual-time-window protocols for quantitative [18F]flutemetamol and [18F]florbetaben PET studies |
| title_short | Optimized dual-time-window protocols for quantitative [18F]flutemetamol and [18F]florbetaben PET studies |
| title_sort | optimized dual time window protocols for quantitative 18f flutemetamol and 18f florbetaben pet studies |
| topic | Amyloid Quantification Simplified methods Flutemetamol PET Florbetaben PET Alzheimer’s disease |
| url | http://link.springer.com/article/10.1186/s13550-019-0499-4 |
| work_keys_str_mv | AT fionaheeman optimizeddualtimewindowprotocolsforquantitative18fflutemetamoland18fflorbetabenpetstudies AT maqsoodyaqub optimizeddualtimewindowprotocolsforquantitative18fflutemetamoland18fflorbetabenpetstudies AT isadoralopesalves optimizeddualtimewindowprotocolsforquantitative18fflutemetamoland18fflorbetabenpetstudies AT kerstinheurling optimizeddualtimewindowprotocolsforquantitative18fflutemetamoland18fflorbetabenpetstudies AT johannesberkhof optimizeddualtimewindowprotocolsforquantitative18fflutemetamoland18fflorbetabenpetstudies AT juandomingogispert optimizeddualtimewindowprotocolsforquantitative18fflutemetamoland18fflorbetabenpetstudies AT santiagobullich optimizeddualtimewindowprotocolsforquantitative18fflutemetamoland18fflorbetabenpetstudies AT christopherfoley optimizeddualtimewindowprotocolsforquantitative18fflutemetamoland18fflorbetabenpetstudies AT adriaanalammertsma optimizeddualtimewindowprotocolsforquantitative18fflutemetamoland18fflorbetabenpetstudies AT onbehalfoftheamypadconsortium optimizeddualtimewindowprotocolsforquantitative18fflutemetamoland18fflorbetabenpetstudies |