June 9, 2015 - Piramal Imaging announced the presentation of additional analyses from its florbetaben phase 3 histopathology study, in which the florbetaben positron emission tomography (PET) signal from binding to morphologically distinct beta-amyloid plaques was examined. The analyses also examined the potential influence of plaques in the reference region for quantification. The results, which were presented at the 2015 annual meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) in Baltimore, provide additional details on the topographic distribution of different beta-amyloid aggregates in the brain and on quantification.
In one analysis, entitled, Impact of Morphologically Distinct Beta-amyloid Deposits on 18F-Florbetaben (FBB) PET Scans, investigators examined florbetaben PET data to investigate the impact of diffuse, neuritic and vascular beta-amyloid deposits on different regions of interest in the brain. They collected brain tissue samples from 87 end-of-life patients (including 64 with Alzheimer's disease [AD], 14 with other dementia, and 9 non-demented aged volunteers; mean age 80.4±10.2 years) who underwent a florbetaben PET scan before death. In the frontal and posterior cingulate cortices - brain regions with high frequency of deposits - both diffuse and neuritic beta-amyloid contributed significantly to 18F-florbetaben uptake. In the occipital and anterior cingulate cortices - brain regions with low deposit frequency - only diffuse beta-amyloid plaques contributed significantly to the uptake. The presence of vascular beta-amyloid deposits contributed significantly to the uptake only in the occipital cortex.
"PET imaging using 18F-florbetaben as a radiotracer may allow for detection of morphologically distinct beta amyloid deposits in the brain aside from neuritic plaques, and their distribution in different brain regions. Further clinical studies are needed to elucidate how these deposits influence and contribute to cognitive impairment and dementia," commented co-author Ana M. Catafau, M.D., Ph.D., vice president of clinical R&D neurosciences at Piramal Imaging. "Findings such as these may provide the requisite detailed information to help researchers better understand the time course and contributions of different types of plaque to the pathogenesis of Alzheimer's disease and other types of cognitive impairment."
In a second analysis, Cerebellar Senile Plaques: How Frequent are They and Do They Influence 18F-florbetaben SUVR?, researchers assessed the influence of cerebellar plaques on signal quantification when the cerebellar cortex is used as a reference region for quantification. Cerebellar beta-amyloid plaques may be present in late-stage AD, and it was previously unknown if these would influence quantification.
Researchers conducted a neuropathological assessment of cerebral (frontal, occipital, anterior and posterior cingulate) cortex and cerebellar cortex tissue from the 87 end-of-life patients who underwent a florbetaben PET scan before death. Presence of neuritic/cored and diffuse plaques was assessed as absent, sparse, moderate and frequent. Mean cortical standardized uptake value ratios (SUVRs) were compared among brains with different cerebellar plaque loads. Results showed the presence of senile plaques in the cerebellum is very infrequent. The cerebellum most frequently shows sparse diffuse plaques, which correspond to brains with higher cerebral cortical beta-amyloid loads. However, the presence of cerebellar senile plaques did not influence the SUVRs in subjects with presence of cerebral cortical beta-amyloid. Therefore, the data suggest the effect of cerebellar senile plaques in 18F-florbetaben SUVR is negligible, even in advanced stages of AD in patients with high cerebral cortical beta-amyloid load.
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April 17, 2024 
