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Imaging characteristics and safety of florbetapir (18F) in Japanese healthy volunteers, patients with mild cognitive impairment and patients with Alzheimer’s disease

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Abstract

Objective

The purpose of this study was to evaluate the performance characteristics and safety of florbetapir (I8F) positron emission tomography (PET) in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) and cognitively normal (CN) control patients from Japan.

Methods

Florbetapir (I8F) PET was obtained in 48 subjects (15 AD patients, 15 MCI patients, and 18 CNs) within a multicenter phase 2/3 study. Amyloid burden was assessed visually and classified as positive or negative for pathologic levels of amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVRs) were determined from the florbetapir (I8F) PET images. Safety was assessed by monitoring adverse events, vital signs, clinical laboratory assessments, and electrocardiograms. Demographic variables and cognitive scales were summarized by using descriptive statistics for each group. Fisher’s exact test and one-way analysis of variance were used to compare amyloid positivity and mean SUVRs, respectively, between diagnostic groups.

Results

Florbetapir (I8F) PET was rated visually amyloid positive in 80.0 % of AD patients, 33.3 % of MCI patients, and 16.7 % of CNs. Mean SUVRs were highest in the AD group and lowest in the CN group for each brain region (P < 0.01) and globally (P < 0.05). Kappa statistics showed strong inter-reader agreement (Fleiss’ kappa = 0.82) and individual reader’s agreement with the majority of readers (kappa ranged from 0.79 to 1.0). Seventeen of the 48 subjects (35.4 %) were Apolipoprotein E genotype ε4 positive, which included 10 subjects in the AD group and 7 subjects in the MCI group. A total of 6 subjects (5 of whom were in the CN group) had at least 1 treatment-emergent adverse event (TEAE).

Conclusions

These data indicate that amyloid positivity increased with diagnostic category (CN < MCI < AD) and are consistent with expected rates of amyloid positivity among individuals with clinical diagnoses of AD and MCI. In addition, these results were similar to those obtained in United States studies. Florbetapir (18F) was safe and well tolerated. The reliability of both qualitative and quantitative assessments of florbetapir (18F) in this study population provides support for potential use in clinical settings in Japan.

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Acknowledgments

We thank the Institute of Biomedical Research and Innovation, The University of Tokyo, and Nippon Medical School; each acted as a contract manufacturer of florbetapir (18F) as an investigational medical product.

We also thank the staff of the all the sites, in particular, Takuya Arai (The University of Tokyo Hospital), Masahiro Sasaki (Institute of Biomedical Research and Innovation), and Kazuyoshi Honjo (Nippon Medical School) for manufacturing and quality control.

Lastly, the authors would like to thank Shannon Gardell, PhD (inVentiv Health Clinical, LLC) for assistance with preparation of the manuscript and Angela Lorio, ELS (inVentiv Health Clinical, LLC) for editorial assistance.

CN was a full-time employee of, and minor stockholder in, Eli Lilly and Company at the time of this work and is now employed by Kyoto University Hospital. YT is a full-time employee of, and minor stockholder in, Eli Lilly and Company. AA, ADJ, ML, and MJP are employees of Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly. CB was an employee of Avid Radiopharmaceuticals at the time of this work and is now employed by Spectrum Dynamics. AI has received research funding from Jannsen Pharmaceuticals. TM has served as a clinical trial representative for and received research funding from Eli Lilly and Company. MS has served as a clinical trial representative for Eli Lilly and Company/Avid Radiopharmaceuticals. YO has received research funding from Quintiles.

This research was totally funded by Eli Lilly and Company and/or any of its subsidiaries.

Author information

Authors and Affiliations

  1. Department of Psychiatry, Kyoto University Hospital, 54 Kawaharacho, Syogoin, Sakyu-ku, Kyoto, 606-8507, Japan

    Chihiro Namiki

  2. Eli Lilly Japan K.K., Kobe, Japan

    Yasushi Takita

  3. Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Atsushi Iwata

  4. Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Toshimitsu Momose

  5. Division of Molecular Imaging, Institute of Biomedical Research and Innovation, Kobe, Japan

    Michio Senda

  6. Department of Neuropsychiatry, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan

    Yoshiro Okubo

  7. Avid Radiopharmaceuticals, Philadelphia, PA, USA

    Abhinay D. Joshi, Ming Lu, Abigail Agbulos, Christopher Breault & Michael J. Pontecorvo

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  1. Chihiro Namiki
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  2. Yasushi Takita
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Correspondence to Chihiro Namiki.

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Trial Registration: NCT01662882.

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Namiki, C., Takita, Y., Iwata, A. et al. Imaging characteristics and safety of florbetapir (18F) in Japanese healthy volunteers, patients with mild cognitive impairment and patients with Alzheimer’s disease. Ann Nucl Med 29, 570–581 (2015). https://doi.org/10.1007/s12149-015-0978-2

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  • DOI: https://doi.org/10.1007/s12149-015-0978-2

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