Abstract
Background[18F]MK-6240 is a PET tracer with sub-nanomolar affinity for neurofibrillary tangles. Therefore, tau quantification is possible with [18F]MK-6240 PET/CT scans, and it can be used for assessment of Alzheimer’s disease. However, long acquisition scans are required to provide fully quantitative estimates of pharmacokinetic parameters. Therefore, on the present study, dual-time-window (DTW) acquisitions was simulated to reduce PET/CT acquisition time, while taking into consideration perfusion changes and possible scanning protocol non-compliance. To that end, time activity curves (TACs) representing a 120-min acquisition (TAC120) were simulated using a two-tissue compartment model with metabolite corrected arterial input function from 90-min dynamic [18F]MK-6240 PET scans of three healthy control subjects and five subjects with mild cognitive impairment or Alzheimer’s disease. Therefore, TACs corresponding to different levels of specific binding were generated and then various perfusion changes were simulated. Next, DTW acquisitions were simulated consisting of an acquisition starting at tracer injection, a break and a second acquisition starting at 90 min post-injection. Finally, non-compliance with the PET/CT scanning protocol were simulated to assess its impact on quantification. All TACs were quantified using reference Logan’s distribution volume ratio (DVR) and standardized uptake value ratio (SUVR90) using the cerebellar cortex as reference region.ResultsIt was found that DVR from a DTW protocol with a 60-min break between two 30-min dynamic scans closely approximates the DVR from the uninterrupted TAC120, with a regional bias smaller than 2.5%. Moreover, SUVR90 estimates were more susceptible (regional bias ≤ 19%) to changes in perfusion compared to DVR from a DTW TAC (regional bias ≤ 10%). Similarly, SUVR90 was affected by late-time scanning protocol delays reaching an increase of 8% for a 20-min delay, while DVR was not affected (regional bias < 1.5%) by DTW protocol non-compliance.ConclusionsTherefore, such DTW protocol has the potential to increase patient comfort and throughput without compromising quantitative accuracy and is more reliable against SUVR in terms of perfusion changes and protocol deviations, which could prove beneficial for drug effect assessment and patient follow-up using longitudinal [18F]MK-6240 PET imaging.
Highlights
Accumulation of neurofibrillary tangles (NFT) is related to cognitive decline and is one of the neuropathological hallmarks of Alzheimer’s disease (AD) [1]
Kolinger et al EJNMMI Res (2021) 11:49 that in-vivo quantification of NFTs may support disease staging and assessing the neurological condition of patients. This can be achieved with positron emission tomography (PET) tracers that bind to hyper-phosphorylated tau proteins, such as [18F]MK-6240 which has sub-nanomolar affinity for NFTs and has been studied and validated recently in healthy control (HC), mild cognitive impairment (MCI), and AD subjects [3,4,5,6,7]
The largest average regional Distribution Volume Ratios (DVR) bias for HC subjects with TACDTW60 and perfusion changes with constant R1 was − 2.2% [− 3.1%:− 1.01%] (p < 0.001, volumes of interest (VOI) 3+, Tracer influx rate from plasma to tissue (K1)-50%) and for MCI/AD subjects it was − 10.1% [− 19.3%:− 0.93%]
Summary
Accumulation of neurofibrillary tangles (NFT) is related to cognitive decline and is one of the neuropathological hallmarks of Alzheimer’s disease (AD) [1]. Kolinger et al EJNMMI Res (2021) 11:49 that in-vivo quantification of NFTs may support disease staging and assessing the neurological condition of patients This can be achieved with positron emission tomography (PET) tracers that bind to hyper-phosphorylated tau proteins, such as [18F]MK-6240 which has sub-nanomolar affinity for NFTs and has been studied and validated recently in healthy control (HC), mild cognitive impairment (MCI), and AD subjects [3,4,5,6,7]. Previous in-human [18F]MK-6240 studies performed dynamic PET scans with a duration up to 180 min and used a reference tissue model with the cerebellum as reference brain region This reference tissue model approach uses the time activity curve (TAC) of a reference tissue assumed to be devoid of specific tracer binding to estimate the ratio of specific to nondisplaceable binding in target regions. Tau pathology and changes in relative CBF have been observed to independently contribute to cognitive deficits in AD [13], emphasizing the need to understand the interplay between tau load, tracer binding, and longitudinal changes in CBF
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