Abstract: Avid Radiopharmaceuticals is currently conducting a phase III clinical study of subjects at the end of
life with and without neurodegenerative dementia. A planned interim analysis of the first six subjects brought to
autopsy has been performed comparing histopathology to quantitative and qualitative assessments of amyloid
PET imaging.
Subjects who were ≥18 years old and willing to consent to a brain autopsy were admitted to the study if they
had a life expectancy of <6 months. Florbetapir F 18 PET imaging was performed at the time of enrollment.
Blinded raters scored the PET images for overall ligand retention in cortical grey matter using a semi-qualitative
(0-4) scale. Mean cortical to cerebellar standard uptake value ratios (SUVr) were also determined across six
predefined regions of interest. The mean interval from imaging to time of death was 43 days (range 1-158).
Neuropathologic studies were performed blinded to the clinical and PET data. At the time of death, 6 micron
paraffin-embedded tissue sections corresponding to the PET regions of interest were evaluated for density of
β-amyloid deposition using immunohistochemistry (Signet 4G8, 100% sampling) and semi-quantitative estimates
of plaque density as determined by a Bielschowsky silver stain of the same regions (modified CERAD scoring:
none, sparse, moderate or frequent).
Of the six subjects, 4 had a clinical diagnosis at the time of imaging of AD, one had a clinical diagnosis of
Parkinson’s disease with dementia (PDD), and one had no clinical evidence of dementia. The mean age was
76 (range 47-86). Histopathology, CERAD neuritic plaque scores, florbetapir PET SUVr values, and visual ratings
of grey matter retention will be presented and compared for the six autopsy cases.
