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Introduction <p>Tau protein aggregation is a hallmark of Alzheimer’s disease (AD) pathology. Semi-quantitative analysis using regions of interest (ROIs)-based standardized uptake value ratios (SUVRs) serves as a major Tau positron emission tomography (PET) biomarker for AD diagnosis and staging. This study aims to evaluate the diagnostic performance of the second-generation tau tracer <sup>18</sup>F-Florzolotau, including the impact of semi-quantitative reference region and ROIs methodology and partial volume error (PVE) correction. Data from the FDA-approved tracer <sup>18</sup>F-Flortaucipir provide benchmark context, aiming to evaluate the performance.</p> Methods <p>A total of 842 participants from two cohorts underwent tau PET imaging with either <sup>18</sup>F-Flortaucipir (<i>n</i> = 741) or <sup>18</sup>F-Florzolotau (<i>n</i> = 101). The <sup>18</sup>F-Flortaucipir cohort contains 384 normal controls, 292 patients with mild cognitive impairment, and 65 AD dementia. The <sup>18</sup>F-Florzolotau cohort contains 27 normal controls, 26 patients with mild cognitive impairment and 48 AD dementia. SUVRs were calculated across four ROIs using six semi-quantitative methods varying by reference region and PVE-correction application. Diagnostic performance was assessed using the area under the curve (AUC) from receiver operating characteristic analysis. Partial correlations between SUVRs and clinical severity were evaluated.</p> Results <p><sup>18</sup>F-Florzolotau demonstrated high diagnostic accuracy (AUC: 0.96–0.98) for AD dementia and strong clinical correlations (|<i>r</i>|= 0.61–0.74). Performance varied with semi-quantitative methodology. The optimal approach used inferior cerebellar gray matter as the reference region, achieving the highest AUC and strong clinical correlations for <sup>18</sup>F-Florzolotau. Results for <sup>18</sup>F-Flortaucipir (AUC: 0.78–0.87; |<i>r</i>|= 0.29–0.45) provided consistent methodological insights supporting the choice of inferior cerebellar gray methodology.</p> Conclusions <p><sup>18</sup>F-Florzolotau shows excellent diagnostic performance for AD dementia. The semi-quantitative methodology impacts results, with inferior cerebellar gray as the recommended reference region for optimizing <sup>18</sup>F-Florzolotau SUVR analysis in AD dementia. These findings support the clinical utility of <sup>18</sup>F-Florzolotau tau PET in AD.</p>

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Evaluating 18F-Florzolotau tau PET for Alzheimer’s disease diagnosis with 18F-Flortaucipir as reference

  • 期刊论文

  • 发表日期：

    2025年8月28日

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  • Qi Zhang,
  • Jiaying Lu,
  • Luyao Wang,
  • Fangyang Jiao,
  • Min Wang,
  • Kuangyu Shi,
  • Chuantao Zuo,
  • Jiehui Jiang

摘要

Introduction

Tau protein aggregation is a hallmark of Alzheimer’s disease (AD) pathology. Semi-quantitative analysis using regions of interest (ROIs)-based standardized uptake value ratios (SUVRs) serves as a major Tau positron emission tomography (PET) biomarker for AD diagnosis and staging. This study aims to evaluate the diagnostic performance of the second-generation tau tracer 18F-Florzolotau, including the impact of semi-quantitative reference region and ROIs methodology and partial volume error (PVE) correction. Data from the FDA-approved tracer 18F-Flortaucipir provide benchmark context, aiming to evaluate the performance.

Methods

A total of 842 participants from two cohorts underwent tau PET imaging with either 18F-Flortaucipir (n = 741) or 18F-Florzolotau (n = 101). The 18F-Flortaucipir cohort contains 384 normal controls, 292 patients with mild cognitive impairment, and 65 AD dementia. The 18F-Florzolotau cohort contains 27 normal controls, 26 patients with mild cognitive impairment and 48 AD dementia. SUVRs were calculated across four ROIs using six semi-quantitative methods varying by reference region and PVE-correction application. Diagnostic performance was assessed using the area under the curve (AUC) from receiver operating characteristic analysis. Partial correlations between SUVRs and clinical severity were evaluated.

Results

18F-Florzolotau demonstrated high diagnostic accuracy (AUC: 0.96–0.98) for AD dementia and strong clinical correlations (|r|= 0.61–0.74). Performance varied with semi-quantitative methodology. The optimal approach used inferior cerebellar gray matter as the reference region, achieving the highest AUC and strong clinical correlations for 18F-Florzolotau. Results for 18F-Flortaucipir (AUC: 0.78–0.87; |r|= 0.29–0.45) provided consistent methodological insights supporting the choice of inferior cerebellar gray methodology.

Conclusions

18F-Florzolotau shows excellent diagnostic performance for AD dementia. The semi-quantitative methodology impacts results, with inferior cerebellar gray as the recommended reference region for optimizing 18F-Florzolotau SUVR analysis in AD dementia. These findings support the clinical utility of 18F-Florzolotau tau PET in AD.