Feasibility of ¹⁸F-florzolotau quantification in patients with Alzheimer's disease based on an MRI-free tau PET template

Jiaying Lu¹, Zizhao Ju¹, Min Wang², Xun Sun³, Chenhao Jia⁴, Ling Li⁵, Weiqi Bao¹, Huiwei Zhang¹, Fangyang Jiao¹, Huamei Lin¹, Tzu-Chen Yen⁶, Ruixue Cui⁷, Xiaoli Lan⁸, Qianhua Zhao^{9

10}, Yihui Guan¹, Chuantao Zuo^{1

11}; Shanghai Memory Study (SMS)

Affiliations

¹ Department of Nuclear Medicine & PET Center & National Center for Neurological Disorders & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
² Institute of Biomedical Engineering, School of Life Science, Shanghai University, Shanghai, China.
³ Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Center for Rare Diseases Research, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
⁵ Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
⁶ APRINOIA Therapeutics Co. Ltd, Suzhou, China.
⁷ Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Center for Rare Diseases Research, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China. mmdhmm@126.com.
⁸ Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. xiaoli_lan@hust.edu.cn.
⁹ Department of Neurology & National Center for Neurological Disorders & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. qianhuazhao@fudan.edu.cn.
¹⁰ MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China. qianhuazhao@fudan.edu.cn.
¹¹ Human Phenome Institute, Fudan University, Shanghai, China.

PMID: 37099173
DOI: 10.1007/s00330-023-09571-7

Feasibility of ¹⁸F-florzolotau quantification in patients with Alzheimer's disease based on an MRI-free tau PET template

Jiaying Lu et al. Eur Radiol. 2023 Jul.

. 2023 Jul;33(7):4567-4579.

doi: 10.1007/s00330-023-09571-7. Epub 2023 Apr 26.

Authors

Affiliations

¹ Department of Nuclear Medicine & PET Center & National Center for Neurological Disorders & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
² Institute of Biomedical Engineering, School of Life Science, Shanghai University, Shanghai, China.
³ Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Center for Rare Diseases Research, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
⁵ Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
⁶ APRINOIA Therapeutics Co. Ltd, Suzhou, China.
⁷ Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Center for Rare Diseases Research, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China. mmdhmm@126.com.
⁸ Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. xiaoli_lan@hust.edu.cn.
⁹ Department of Neurology & National Center for Neurological Disorders & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. qianhuazhao@fudan.edu.cn.
¹⁰ MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China. qianhuazhao@fudan.edu.cn.
¹¹ Human Phenome Institute, Fudan University, Shanghai, China.

PMID: 37099173
DOI: 10.1007/s00330-023-09571-7

Abstract

Objectives: Quantification of tau accumulation using positron emission tomography (PET) is critical for the diagnosis of Alzheimer's disease (AD). This study aimed to evaluate the feasibility of ¹⁸F-florzolotau quantification in patients with AD using a magnetic resonance imaging (MRI)-free tau PET template, since individual high-resolution MRI is costly and not always available in practice.

Methods: ¹⁸F-florzolotau PET and MRI scans were obtained in a discovery cohort including (1) patients within the AD continuum (n = 87), (2) cognitively impaired patients with non-AD (n = 32), and (3) cognitively unimpaired subjects (n = 26). The validation cohort comprised 24 patients with AD. Following MRI-dependent spatial normalization (standard approach) in randomly selected subjects (n = 40) to cover the entire spectrum of cognitive function, selected PET images were averaged to create the ¹⁸F-florzolotau-specific template. Standardized uptake value ratios (SUVRs) were calculated in five predefined regions of interest (ROIs). MRI-free and MRI-dependent methods were compared in terms of continuous and dichotomous agreement, diagnostic performances, and associations with specific cognitive domains.

Results: MRI-free SUVRs had a high continuous and dichotomous agreement with MRI-dependent measures for all ROIs (intraclass correlation coefficient ≥ 0.980; agreement ≥ 94.5%). Similar findings were observed for AD-related effect sizes, diagnostic performances with respect to categorization across the cognitive spectrum, and associations with cognitive domains. The robustness of the MRI-free approach was confirmed in the validation cohort.

Conclusions: The use of an ¹⁸F-florzolotau-specific template is a valid alternative to MRI-dependent spatial normalization, improving the clinical generalizability of this second-generation tau tracer.

Key points: • Regional ¹⁸F-florzolotau SUVRs reflecting tau accumulation in the living brains are reliable biomarkers for the diagnosis, differential diagnosis, and assessment of disease severity in patients with AD. • The ¹⁸F-florzolotau-specific template is a valid alternative to MRI-dependent spatial normalization, improving the clinical generalizability of this second-generation tau tracer.

Keywords: Alzheimer’s disease; Magnetic resonance imaging; Positron emission tomography; Tau proteins.

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Comment in

Commentary: Application of automatic semi-quantification in clinical routine positron emission tomography brain studies is here to stay.
Oliveira FPM, Costa DC. Oliveira FPM, et al. Eur Radiol. 2023 Jul;33(7):4564-4566. doi: 10.1007/s00330-023-09637-6. Epub 2023 Apr 13. Eur Radiol. 2023. PMID: 37351691 No abstract available.

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Feasibility of ¹⁸F-florzolotau quantification in patients with Alzheimer's disease based on an MRI-free tau PET template

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Feasibility of ¹⁸F-florzolotau quantification in patients with Alzheimer's disease based on an MRI-free tau PET template

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