Imaging of amyloid beta in Alzheimer's disease with (18)F-BAY94-9172, a novel PET tracer: proof of mechanism
Rowe CC, Ackerman U, Browne W, Mulligan R, Pike KL, O'Keefe G, et al.;
Commented by , 26 Feb 2008
Aim of the study
To find a PET marker that will be reliable to diagnose Alzheimer's disease (AD) in early stage, with clear differentiation between normal subjects and patients with frontotemporal lobar degeneration (FTLD). This marker should be available to more clinical diagnostic and research centers because of its longer half-life.
Method
15 patients with AD (classic NINCDS-ADRDA + DSM-IV criteria for dementia; MMSE 23.3±4), 5 with FTDL and 15 healthy elderly controls were compared using PET scanning with the A ß ligand 18F-BAY94-9172, quantification being achieved by a standardized uptake value ratio (SUVR) calculated for the neocortex by use of the cerebellum as reference region.
Results
18F-BAY94-9172 binding matched the reported post-mortem distribution of A ß plaques, with widespread neocortical binding in the patients with AD, greater in the precuneus/posterior cingulate and frontal cortex than in the lateral temporal and parietal cortex. At 90-120 minutes post injection, the SUVR for AD was 2.0, controls 1.3 (p<0.001) and FTLD 1.2 (p=0.009). Visual interpretation as normal or AD was 100% sensitive and 90% specific.
Professor Gauthier's comments
This publication is important because is describes a PET maker that may be as sensitive as 11C-PIB, but with a longer half-life that will allow for use in many centers world-wide, allowing for faster validation of the concept of "predementia stage" of AD ref. 1, a stage where there are no standard symptomatic treatments, allowing in principle randomized placebo-controlled studies with potential disease-modifying drugs. The other PET marker recommended is 18F-deoxyglucose. Thus two 18F labeled markers would now be available for early AD diagnosis.
Another recent findings in the field of brain imaging and early AD is the observation that higher educated persons have more amyloid binding and less glucose metabolism compared to low educated patients, in accordance with the brain cognitive reserve hypothesis ref. 2.
Early diagnosis of dementia with Lewy Bodies may also be possible using brain scintigraphy of the striatal dopamine transporter system using FP-CIT SPECT and cardiac scintigraphy using 123I-MIBG ref. 3. Readers interested in a general review of the neuroimaging field will enjoy Small et al. ref. 4, and those interested in neurochemical and imaging biomarkers of AD will enjoy Hampel et al. ref. 5.
It is likely that these biomarkers will allow for early diagnosis of AD, with new ethical and clinical challenges, but offering the possibility of early treatment that will effectively modify disease progression.
References
1. Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurology 2007; 6 (8); 734-746
2. Kemppainen NM, Aalto S, Karrasch M, Någren K, Savisto N, Oikonen V, et al. Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild AD. Annals of Neurology 2008; 63 (1); 112-118
3. Aarsland D, Kurz M, Beyer M, Bronnick K, Piepenstock SN, Ballard C. Early Discriminatory Diagnosis of Dementia with Lewy Bodies. Dementia and Geriatric Cognitive Disorders 2008; 25; 195-205. [DOI: 10.1159/000113417]
4. Small GW, Bookheimer SY, Thompson PM, Cole GM, Huang S-C, Kepe V et al. Current and future uses of neuroimaging for cognitively impaired patients. Lancet Neurology 2008; 7 (2); 161-172
5. Hampel H, Bürger K, Teipel SJ, Bokde ALW, Zetterberg H, Blennow K. Core candidate neurochemical and imaging biomarkers of Alzheimer's disease. Alzheimer's & Dementia 2008; 4 (1); 38-48