• Cognitive Disorders
• Neuroimaging
• Tomography
• Dementias Clinical Trials

• Cognitive Disorders
• Neuroimaging
• Tomography
• Neurology
• Dementias
• Neurology Clinical Trials

There is a strong correlation between florbetaben (an F-labeled β-amyloid-targeted tracer) uptake and amyloid pathology, according to Marwan Sabbagh, MD, Banner Sun Health Research Institute, Sun City, Arizona, USA, who presented results of the Phase III Study of Florbetaben (BAY94-9172) PET Imaging for Detection/Exclusion of Cerebral β-Amyloid Compared to Histopathology trial (ClinicalTrials.gov identifier NCT01020838). These results support the use of florbetaben as a valuable diagnostic tool for the exclusion of Alzheimer's disease (AD) or differential diagnosis of dementia as the cause of cognitive decline.

Florbetaben has recently been approved as an adjunct to other diagnostic evaluations for positron emission tomographic (PET) imaging of the brain to estimate β-amyloid neuritic plaque density in adults with cognitive impairment who are being evaluated for AD and other causes of cognitive decline.

The aim of researchers in the present analysis was to assess the diagnostic efficacy of florbetaben and its negative predictive value in a large histopathology cohort of subjects who underwent antemortem florbetaben PET imaging. The analysis was based on data from the aforementioned large Phase 3 multicenter nonrandomized trial in 205 end-of-life subjects who underwent PET imaging 90 to 110 minutes after receiving an intravenous injection of florbetaben 300 MBq (±20%). Brain samples were obtained at autopsy and assessed for neuritic β-amyloid plaques using the Consortium for Establishing a Registry for Alzheimer's Disease criteria. PET images were assessed by 3 independent readers masked to the clinical diagnosis and all other clinical findings and quantitatively by using preestablished brain volumes of interest to obtain standardized uptake value ratios (SUVRs), taking the cerebellar cortex as the reference region.

As of the date of this analysis, 74 subjects had died. The antemortem clinical diagnoses for these subjects included AD (n=57), dementia with Lewy bodies (n=3), not demented (n=8), and other dementia (n=6). Postmortem, it was noted that the clinical diagnosis of AD was incorrect in 23% of cases (13 of 57). Histopathology confirmed the presence of β-amyloid in 47 of the 74 subjects; no β-amyloid plaques were found in 27 subjects (Table 1).

Of the 27 patients in whom no β-amyloid plaques were found, 4 had no neurodegenerative pathologies and were correctly read as negative on PET imaging; 23 had non-AD neurodegenerative pathologies. Twenty of these 23 non-AD neurodegenerative scans were correctly read as negative on PET imaging.

Scans from 46 of the 47 subjects with β-amyloid were correctly read as positive, yielding sensitivity of 98%. Scans from 24 of the 27 subjects without β-amyloid were correctly read, yielding specificity of 89%. Twenty-four of 25 scans read as negative were correctly assessed, yielding a negative predictive value of 96%.

For the quantitative analysis, SUVR analysis showed good discrimination of the PET signal between the presence and absence of β-amyloid. The mean composite SUVR values were 1.71±0.27 for the presence of β-amyloid and 1.24±0.18 for the absence of β-amyloid. A receiver operating characteristic curve analysis indicated that an SUVR of 1.478 was the optimal cutoff for the calculation of sensitivity (89%) and specificity (92%).

Dr. Sabbagh concluded these data support the value of florbetaben as a diagnostic marker for AD and that negative results on a florbetaben scan should encourage clinicians to search for other causes of cognitive decline.

• © 2014 MD Conference Express®