[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

• Published in: Acta neuropathologica Vol. 124; no. 6; pp. 833 - 845
• 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: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.12.2012
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - complications; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Amyloid - metabolism; Amyloid beta-Peptides - metabolism; Aniline Compounds; Benzothiazoles; Biopsy - methods; Brain - diagnostic imaging; Brain - pathology; Female; Humans; Hydrocephalus, Normal Pressure - complications; Hydrocephalus, Normal Pressure - diagnostic imaging; Hydrocephalus, Normal Pressure - pathology; Male; Medicine; Medicine & Public Health; Middle Aged; Neurosciences; Original Paper; Pathology; Plaque, Amyloid - pathology; Positron-Emission Tomography; Prospective Studies; Retrospective Studies; Brain biopsy; Alzheimer’s disease; Normal pressure hydrocephalus; Fibrillar amyloid β; [; F]Flutemetamol; Positron emission 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 β positron emission tomography (PET) imaging agent [ 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 β 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) [ 18 F]flutemetamol PET imaging for detection of cerebral cortical fibrillar amyloid β and cortical brain biopsy during intracranial pressure measurement or ventriculo-peritoneal shunting. [ 18 F]Flutemetamol uptake was quantified using standardized uptake value ratio (SUVR) with cerebellar cortex as the reference region. Tissue fibrillar amyloid β 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 [ 18 F]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 β were similar. Blinded image evaluation showed strong agreement between readers ( κ  = 0.86). Overall sensitivity and specificity by majority read were 93 and 100 %. Noninvasive in vivo [ 18 F]flutemetamol PET imaging demonstrates strong concordance with histopathology for brain fibrillar amyloid β, 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.