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Purpose  The simplified reference tissue model (SRTM) is commonly applied for the quantification of brain positron emission tomography (PET) studies, particularly because it avoids arterial cannulation. SRTM requires a validated reference region which is obtained by baseline-blocking or displacement studies. Once a reference region is validated, the use should be verified for each new subject. This verification normally requires volume of distribution ( V  T ) of a reference region. However, performing dynamic scanning and arterial sampling is not always possible, specifically in elderly subjects and in advanced disease stages. The aim of this study was to investigate the use of non-invasive standardised uptake value (SUV) approaches, in comparison to  V  T , as a verification of the previously validated grey matter cerebellum reference region for [ 18 F]flortaucipir and [ 18 F]florbetapir PET imaging in Alzheimer’s disease (AD) patients and controls.    Procedures  Dynamic 130-min [ 18 F]flortaucipir PET scans obtained from nineteen subjects (10 AD patients) and 90-min [ 18 F]florbetapir dynamic scans obtained from fourteen subjects (8 AD patients) were included. Regional  V  T ’s were estimated for both tracers and were considered the standard verification of the previously validated reference region. Non-invasive SUVs corrected for body weight (SUV BW ), lean body mass (SUL), and body surface area (SUV BSA ) were obtained by using later time intervals of the dynamic scans. Simulations were also performed to assess the effect of flow and specific binding (BP ND ) on the SUVs.    Results  A low SUV corresponded well with a low  V  T  for both [ 18 F]flortaucipir and [ 18 F]florbetapir. Simulation confirmed that SUVs were only slightly affected by flow changes and that increases in SUV were predominantly determined by the presence of specific binding.    Conclusions  In situations where dynamic scanning and arterial sampling is not possible, a low SUV (80–100 min)  for [ 18 F]flortaucipir and a low SUV (50–70 min)  for [ 18 F]florbetapir may be used as indication for absence of specific binding in the grey matter cerebellum reference region.    Supplementary Information  The online version contains supplementary material available at 10.1007/s11307-020-01572-y.

molecular imaging and biology

Non-invasive Standardised Uptake Value for Verification of the Use of Previously Validated Reference Region for [18F]Flortaucipir and [18F]Florbetapir Brain PET Studies