Abstract
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Objectives To determine the degree of association between uptake of [18F]flutemetamol and the level of amyloid-β measured by immunohistochemical (IHC) and histochemical (HC) staining in a frontal or parietal cortical region biopsy site.
Methods Forty nine patients with suspected Normal Pressure Hydrocephalus (NPH) underwent prospective (n=27) or retrospective (n=22) [18F]flutemetamol PET and cortical brain biopsy during intracranial pressure measurement or ventriculo-peritoneal shunting. [18F]Flutemetamol uptake was quantified as a standardized uptake value ratio (SUVR) with cerebellar cortex as a reference region. Tissue amyloid-β was evaluated using the monoclonal antibody 4G8, Thioflavin-S and Bielschowsky silver stain, and an overall pathology result.
Results [18F]Flutemetamol SUVRs from the biopsy site were significantly associated with biopsy specimen amyloid-β levels using 4G8. There was also good correlation between the biopsy amyloid-β level and uptake of [18F]flutemetamol in the region contralateral to the biopsy site, or with composite [18F]flutemetamol uptake. Blinded visual assessment (BVA) of images showed a high level of agreement between all readers. Using the overall pathology result as the standard of truth, BVA of PET images showed overall sensitivity of 93% by majority read; specificity was 100% for each reader.
Conclusions [18F]Flutemetamol (PET imaging agent derived from [11C]PiB) uptake demonstrated strong concordance with in vivo amyloid-β biopsy in patients with NPH irrespective of timing and sequence of examinations in both prospective and retrospective settings, and shows promise as an imaging tool for detection of amyloid-β both in patients with suspected NPH, and possibly in the wider population.
Research Support The study was funded by GE Healthcare, Princeton, NJ