AbstractBackgroundThe accumulation of pathologically misfolded tau is a feature that is shared by a group of neurodegenerative disorders that are collectively referred to as tauopathies. AD is the most prevalent of these tauopathies. Neurofibrillary tangles are characterized by the presence of hyperphosphorylated protein (tau), and senile plaques are characterized by the presence of amyloid peptide aggregates. PET imaging is fully quantitative and enables accurate spatial assessment. However, as a result of non‐specific binding and the limited spatial resolution of PET scanners, this technique requires not only the presence of tau inclusions in a brain region but also sufficient density and spatial extent of those inclusions in order to generate a sufficient signal‐to‐noise ratio. With the development of tau‐specific ligands for use with PET, it is now possible to investigate the role that tau pathology plays in the development and progression of these disorders. The purpose of this study is to analyze, compare, and rank the currently available tau PET tracers for imaging in research and routine clinical settings.MethodWe proposed using the fuzzy Preference Ranking Organization Method for Enrichment of Evaluations (PROMETHEE), a multicriteria decision‐making (MCDM) tool. First‐generation tau PET tracers ([18F]AV1451, [11C]PBB3, [18F]THK5117, [18F]THK5351, [18F]THK5317, and [18F]THK5105) and second‐generation compounds ([18F]MK‐6240, [18F]JNJ‐067, [18F] PI‐2620, [18F]RO‐948 (previously referred to as [18F]RO69558948), [18F]PM‐PBB3, [18F]GTP1, [18F]JNJ‐64349311 ([18F]JNJ311), [11C]RO‐6931643, and [11C]RO‐6924963) were selected to investigate in this study. The evaluation is based on relative parameters, such as specificity, target binding accuracy, neocortical uptake, radiation exposure, brain penetration, free fraction in plasma, defluorination, and adverse reactions, and the importance that is placed on each of these parameters is weighted differently.ResultThe results from this study show that [18F]RO‐948 is the most favorable tau PET ligand, while[18F]THK5105 is the least favorable one based on the considered weighted criteria in this study.ConclusionFuzzy PROMETHEE can be used as a decision‐aid system to select the proper radiopharmaceuticals for tau PET imaging. This study can be extended to include more tracers and criteria and might help researchers and concerned readers to select the optimal tau PET tracer.