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Imaging characteristic of dual-phase 18F-florbetapir (AV-45/Amyvid) PET for the concomitant detection of perfusion deficits and beta-amyloid deposition in Alzheimer’s disease and mild cognitive impairment

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Abstract

Purpose

We investigated dual-phase 18F-florbetapir (AV-45/Amyvid) PET imaging for the concomitant detection of brain perfusion deficits and beta-amyloid deposition in patients with Alzheimer’s disease (AD) and amnestic mild cognitive impairment (MCI), and in cognitively healthy controls (HCs).

Methods

A total of 82 subjects (24 AD patients, 44 MCI patients and 14 HCs) underwent both dual-phase 18F-AV-45 PET and MRI imaging. Dual-phase dynamic PET imaging consisted of (1) five 1-min scans obtained 1 – 6 min after tracer injection (perfusion 18F-AV-45 imaging, pAV-45), and (2) ten 1-min scans obtained 50 – 60 min after tracer injection (amyloid 18F-AV-45 imaging). Amyloid-negative MCI/AD patients were excluded. Volume of interest analysis and statistical parametric mapping of pAV-45 and 18F-AV-45 images were performed to investigate the perfusion deficits and the beta-amyloid burden in the three study groups. The associations between Mini-Mental State Examination (MMSE) scores and global perfusion deficits and amyloid deposition were investigated with linear and segmental linear correlation analyses.

Results

HCs generally had normal pAV-45 findings, whereas perfusion deficits were evident in the hippocampus, and temporal, parietal and middle frontal cortices in both MCI and AD patients. The motor-sensory cortex was relatively preserved. MMSE scores in the entire study cohort were significantly associated with the degree of perfusion impairment as assessed by pAV-45 imaging (r = 0.5156, P < 0.0001). 18F-AV-45 uptake was significantly higher in AD patients than in the two other study groups. However, the correlation between MMSE scores and 18F-AV-45 uptake in MCI patients was more of a binary phenomenon and began in MCI patients with MMSE score 23.14 when 18F-AV-45 uptake was higher and MMSE score lower than in patients with early MCI. Amyloid deposition started in the precuneus and the frontal and temporal regions in early MCI, ultimately reaching the maximum burden in advanced MCI.

Conclusion

Our results indicate that brain perfusion deficits and beta-amyloid deposition in AD follow different trajectories that can be successfully traced using dual-phase 18F-AV-45 PET imaging.

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Acknowledgments

We thank Avid Radiopharmaceuticals Inc. (Philadelphia, PA, USA) for providing the precursor for the preparation of 18F-florbetapir.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine and Molecular Imaging Center, Linkou Chang Gung Memorial Hospital and University, 5. Fu-Hsing Street, Kuei Shan Hsiang, Taoyuan, Taiwan

    Kun-Ju Lin, Ing-Tsung Hsiao, Chia-Ju Hsieh, Shiaw-Pyng Wey & Tzu-Chen Yen

  2. Department of Medical Imaging and Radiological Sciences and Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan

    Kun-Ju Lin, Ing-Tsung Hsiao, Chia-Ju Hsieh, Shiaw-Pyng Wey & Tzu-Chen Yen

  3. Section of Dementia and Cognitive Impairment, Department of Neurology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

    Jung-Lung Hsu

  4. Graduate Institute of Humanities in Medicine, Taipei Medical University, Taipei, Taiwan

    Jung-Lung Hsu

  5. Department of Neurology, Linkou Chang Gung Memorial Hospital and University, Taoyuan, Taiwan

    Chin-Chang Huang & Kuo-Lun Huang

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  1. Kun-Ju Lin
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Correspondence to Kun-Ju Lin.

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Funding

This study was carried out with financial support from the National Research Program for Biopharmaceuticals, National Science Council, Taiwan (MOST 103-2314-B-182A-009, 104-2314-B-182A-083-MY2, 103-2325-B-182A-009) and grants from the Research Fund of Chang Gung Memorial Hospital (CMRPG390793).

Conflicts of Interest

None.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study. In addition, the next of kin or guardians of AD and MCI patients also gave their written informed consent if the patients could not comprehend the study protocol or they could not sign their name clearly.

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Lin, KJ., Hsiao, IT., Hsu, JL. et al. Imaging characteristic of dual-phase 18F-florbetapir (AV-45/Amyvid) PET for the concomitant detection of perfusion deficits and beta-amyloid deposition in Alzheimer’s disease and mild cognitive impairment. Eur J Nucl Med Mol Imaging 43, 1304–1314 (2016). https://doi.org/10.1007/s00259-016-3359-8

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