Optimized dual-time-window protocols for quantitative [18F]flutemetamol and [18F]florbetaben PET studies
| Main Authors: | Fiona Heeman, Maqsood Yaqub, Isadora Lopes Alves, Kerstin Heurling, Johannes Berkhof, Juan Domingo Gispert, Santiago Bullich, Christopher Foley, Adriaan A. Lammertsma |
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| Format: | Article Journal |
| Terbitan: |
, 2019
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| Subjects: | |
| Online Access: |
https://zenodo.org/record/4680176 |
Daftar Isi:
- 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.
- The project leading to this application has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115952. This Joint Undertaking receives the support from the European Union's Horizon 2020 research and innovation program and EFPIA http://www.imi.europa.eu. Juan D. Gispert holds a 'Ramón y Cajal' fellowship (RYC-2013-13054) from the Spanish Ministry of Science, Innovation and Universities. This publication solely reflects the author's view and neither IMI nor the European Union, and EFPIA are responsible for any use that may be made of the information contained herein.