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.
Ann Nucl Med
; 31(3): 260-272, 2017 Apr.
Article
en En
| MEDLINE
| ID: mdl-28181118
ABSTRACT
OBJECTIVE:
This Phase 2 study assessed the performance of positron emission tomography (PET) brain images made with Flutemetamol F 18 Injection in detecting ß-amyloid neuritic plaques in Japanese subjects.METHODS:
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.RESULTS:
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.CONCLUSIONS:
The detection of brain neuritic plaques in Japanese subjects using [18F]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. TRIAL REGISTRATION Clinicaltrials.gov registration number NCT02813070.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
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Tomografía de Emisión de Positrones
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Benzotiazoles
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Enfermedad de Alzheimer
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Disfunción Cognitiva
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Compuestos de Anilina
Tipo de estudio:
Clinical_trials
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Prognostic_studies
Límite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
País/Región como asunto:
Asia
Idioma:
En
Año:
2017
Tipo del documento:
Article