[18F]Flutemetamol PET imaging and cortical biopsy histopathology for fibrillar amyloid β detection in living subjects with normal pressure hydrocephalus: pooled analysis of four studies

Molecular imaging techniques developed to 'visualize' amyloid in vivo represent a major achievement in Alzheimer's disease (AD) research. This pooled analysis of four studies determined the level of association between uptake of the fibrillar amyloid beta positron emission tomography (PET) imaging agent [F-18]flutemetamol (Pittsburgh Compound B analog with a 5.5 times longer half-life to enable it to be used in the clinical setting) and neuritic plaques and fibrillar amyloid beta measured by pathologic staining of cortical region biopsy samples. Fifty-two patients with suspected normal pressure hydrocephalus underwent prospective (n = 30) or retrospective (n = 22) [F-18]flutemetamol PET imaging for detection of cerebral cortical fibrillar amyloid beta and cortical brain biopsy during intracranial pressure measurement or ventriculo-peritoneal shunting. [F-18]Flutemetamol uptake was quantified using standardized uptake value ratio (SUVR) with cerebellar cortex as the reference region. Tissue fibrillar amyloid beta was evaluated using immunohistochemical monoclonal antibody 4G8 and histochemical agents Thioflavin S and Bielschowsky silver stain, and an overall pathology result based on all available immunohistochemical and histochemical results. Biopsy site and contralateral [F-18]flutemetamol SUVRs were significantly associated with neuritic plaque burden assessed with Bielschowsky silver stain (r (spearman's) = 0.61, p = 0.0001 for both), as was the composite SUVR with biopsy pathology (r (spearman's) = 0.74, p < 0.0001). SUVR and immunohistochemical results with 4G8 for detecting fibrillar amyloid beta were similar. Blinded image evaluation showed strong agreement between readers (kappa = 0.86). Overall sensitivity and specificity by majority read were 93 and 100 %. Noninvasive in vivo [F-18]flutemetamol PET imaging demonstrates strong concordance with histopathology for brain fibrillar amyloid beta, supporting its promise as a tool to assist physicians with earlier detection of the disease process and making diagnostic decisions about concomitant AD and other diseases associated with brain amyloidosis.