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

• Published in: Acta neuropathologica 2012-12, Vol.124 (6), p.833
• Main Authors: Rinne, Juha O, Wong, Dean F, Wolk, David A, Leinonen, Ville, Arnold, Steven E, Buckley, Chris, Smith, Adrian, Mclain, Richard, Sherwin, Paul F, Farrar, Gill, Kailajärvi, Marita, Grachev, Igor D
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Biopsy; Brain research; Dementia; Disease; Histopathology; Hydrocephalus; Intracranial pressure; Pathology; Stains & staining; Tomography
• ISSN: 0001-6322; 1432-0533
• DOI: 10.1007/s00401-012-1051-z

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 [^sup 18^F]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) [^sup 18^F]flutemetamol PET imaging for detection of cerebral cortical fibrillar amyloid [beta] and cortical brain biopsy during intracranial pressure measurement or ventriculo-peritoneal shunting. [^sup 18^F]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 [^sup 18^F]flutemetamol SUVRs were significantly associated with neuritic plaque burden assessed with Bielschowsky silver stain (r ^sub spearman's^ = 0.61, p = 0.0001 for both), as was the composite SUVR with biopsy pathology (r ^sub 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 [^sup 18^F]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.[PUBLICATION ABSTRACT]