230 Chapter 9 Methodological applications of [18F]flortaucipir PET The fact that tau pathology is a key pathological factor in AD is indisputable and the anti-tau therapy landscape is rapidly evolving. Currently multiple trials aiming at altering the translational modification of tau, tau immunotherapy, tau aggregation inhibitors, and targeting production of tau and reduction of intracellular tau levels are ongoing. Tau PET markers hold potential for optimizing such clinical trials by selecting the right participants, providing evidence of target engagement, and monitoring treatment effects [1]. However, some challenges need to be addressed before tau PET reaches its full potential. Some of these challenges consider methodological aspects of tau PET, which need to be addressed to optimize its impact. Tau PET acquisition protocols In the context of acquisition protocols an evident question is whether (and when) to use dynamic or static protocols. Although static acquisition protocols have several practical advantages compared to dynamic acquisition protocols (such as computational simplicity and limited patient burden) studies using PET tracers for amyloid pathology demonstrated parameters obtained from dynamically acquired scans are more quantitatively accurate [2, 3]. Considering the application of tau PET in clinical trials, where tau PET serves a crucial role in evaluating drug-efficacy for example, quantitative accuracy is essential. However, applicability of dynamic tau PET in the context of AD is hampered by the long (i.e. 110 min dynamic versus ~20 min static) acquisition time. In order to address this limiting factor of acquisition time we set out to assess whether the dynamic acquisition protocol could be shortened, while maintaining quantitative accuracy in chapter two. We found that for [18F]flortaucipir expanding the break in the dual-time-window protocol with just a 50-min overall scanning time (early interval of 0–30 min, then a coffee break, followed by a late interval of 80–100 min) yielded excellent quantitative accuracy. The optimal shortened dual-time-window protocol (0–30/80–100 min) allows sufficiently accurate estimation of tau load while reducing patient burden and enables interleaved scanning, where other patients could use the camera during breaks within the scan period. A study into amyloid tracers similarly showed that the introduction of a gap with a maximum of 60 min in a dual-time-window protocol (early interval of 0–30 min followed by a late interval of 90–110 min) does not affect quantitative accuracy for [18F]flutemetamol and [18F]florbetaben [4]. Although with a shortened scan duration only 50-min scanning time is required, this is still 30 min more than that required for a static scan and thus static scanning is often still preferred in this regard. However, it is important to realize that static measures are semi-quantitative. Moreover, a study into an amyloid tracer ([11C]PiB) showed that static measures such as SUVr might be effected by blood flow changes overtime in AD, and hence
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