Title |
Brain uptake and safety of Flutemetamol F 18 injection in Japanese subjects with probable Alzheimer’s disease, subjects with amnestic mild cognitive impairment and healthy volunteers
|
---|---|
Published in |
Annals of Nuclear Medicine, February 2017
|
DOI | 10.1007/s12149-017-1154-7 |
Pubmed ID | |
Authors |
Takami Miki, Hiroyuki Shimada, Jae-Seung Kim, Yasuji Yamamoto, Masakazu Sugino, Hisatomo Kowa, Kerstin Heurling, Michelle Zanette, Paul F. Sherwin, Michio Senda |
Abstract |
This Phase 2 study assessed the performance of positron emission tomography (PET) brain images made with Flutemetamol F 18 Injection in detecting β-amyloid neuritic plaques in Japanese subjects. Seventy subjects (25 with probable Alzheimer's disease (pAD), 20 with amnestic mild cognitive impairment (aMCI), and 25 cognitively normal healthy volunteers[HVs]) underwent PET brain imaging after intravenous Flutemetamol F 18 Injection (185 MBq). Images were interpreted as normal or abnormal for neuritic plaque density by each of five non-Japanese and five Japanese readers who were blinded to clinical data. The primary efficacy analysis (based on HV and pAD data) was the agreement of the non-Japanese readers' image interpretations with the clinical diagnosis, resulting in estimates of positive percent agreement (PPA; based on AD subjects; similar to sensitivity) and negative percent agreement (NPA; based on HVs; similar to specificity). Secondary analyses included PPA and NPA for the Japanese readers; inter-reader agreement (IRA); intra-reader reproducibility (IRR); quantitative image interpretations (standardized uptake value ratios [SUVRs]) by diagnostic subgroup; test-retest variability in five pAD subjects; and safety. PPA was 92% for all non-Japanese readers and ranged from 88 to 92% for the Japanese readers. NPA ranged from 96 to 100% for both the non-Japanese readers and the Japanese readers. The majority image interpretations (the interpretations made independently by ≥3 of 5 readers) resulted in PPA values of 92 and 92% and NPA values of 100 and 96% for the non-Japanese and Japanese readers, respectively. IRA and IRR were strong. Composite SUVR values (mean of multiple regional values) allowed clear differentiation between pAD subjects and HVs. Test-retest variability ranged from 1.14 to 2.27%, and test-retest agreement of the blinded visual interpretations was 100% for all readers. Flutemetamol F 18 Injection was generally well tolerated. The detection of brain neuritic plaques in Japanese subjects using [(18)F]Flutemetamol PET images gave results highly consistent with clinical diagnosis, with non-Japanese and Japanese readers giving similar results. Inter-reader agreement and intra-reader reproducibility were high for both sets of readers. Visual delineation of abnormal and normal scans was corroborated by quantitative assessment, with low test-retest variability. Clinicaltrials.gov registration number NCT02813070. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Argentina | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 65 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Bachelor | 10 | 15% |
Researcher | 9 | 14% |
Student > Ph. D. Student | 8 | 12% |
Student > Master | 4 | 6% |
Student > Doctoral Student | 3 | 5% |
Other | 11 | 17% |
Unknown | 20 | 31% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 22 | 34% |
Neuroscience | 6 | 9% |
Nursing and Health Professions | 5 | 8% |
Biochemistry, Genetics and Molecular Biology | 2 | 3% |
Psychology | 1 | 2% |
Other | 6 | 9% |
Unknown | 23 | 35% |