. Longitudinal amyloid imaging using [11C]PIB: Choosing the right method. Human Amyloid Imaging 2011 Meeting Abstracts. 2011 Jan 15;

Abstract:

This work was financially supported by the Internationale Stichting Alzheimer Onderzoek (ISAO, grant 05512), the American Health Assistance Foundation (AHAF, grant A2005-026) and the FP6 network of excellence DiMI (LSH-2003-1.2.2.-2).

Objective: To assess the effects of different analytical methods on observed changes in [11C]PIB binding over time.

Methods: Data from repeat (i.e. baseline and follow-up (FU)) dynamic 90 minutes [11C]PIB PET scans of 7 Alzheimer's disease (AD) patients, 11 patients with Mild Cognitive Impairment (MCI) and 11 healthy controls were used (mean FU: 30}5 months). PET scanning was performed as previously described.1 Global cortical binding values were derived using standardised uptake values for the interval 60-90 min after injection (SUVr), reference Logan2 and RPM23 (basis function implementation of the simplified reference tissue model). RPM2 provides nondisplaceable binding potential (BPND). For the present comparison, however, results were expressed as BPND+1, as this corresponds to the outcome using reference Logan (DVR; distribution volume ratio) and SUVr. For each method percentage change between baseline and FU was calculated.

Results: SUVr values at baseline and FU were on average 12% higher than values obtained with RPM2 and 19% higher than values obtained with reference Logan. Percentage change between baseline and FU differed substantially between methods, especially in AD patients where SUVr (mean}SD) changed with -4}8%, while RPM2 and reference Logan values were relatively stable (0}6 and -1}5%, respectively). Differences were less pronounced in controls and MCI patients (SUVr: 3}4, 8}9%; RPM2: 2}3, 6}7%; reference Logan: 2}3, 5}6%. respectively for controls and MCI).

Conclusion: These data emphasize that for longitudinal imaging, data analysis using quantitative methods such as RPM2 and reference Logan, and thus 90 minutes dynamic scanning, is essential. The decrease at FU in SUVr values for AD patients suggests that this method is biased by factors associated with progression of disease, possibly heterogeneous flow effects. This has important implications, especially for the evaluation of efficacy of novel drugs aimed to lower amyloid load in the brain.

References
1. Tolboom N, Yaqub M, van der Flier WM, Boellaard R, Luurtsema G, Windhorst AD, Barkhof F, Scheltens P, Lammertsma AA, van Berckel BN. Detection of Alzheimer pathology in vivo using both 11C-PIB and 18F-FDDNP PET. J Nucl Med. 2009 Feb;50(2):191-7. Abstract

2. Logan J, Fowler JS, Volkow ND, Wang GJ, Ding YS, Alexoff DL. Distribution volume ratios without blood sampling from graphical analysis of PET data. J Cereb Blood Flow Metab. 1996 Sep;16(5):834-40. Abstract

3. Wu Y, Carson RE. Noise reduction in the simplified reference tissue model for neuroreceptor functional imaging. J Cereb Blood Flow Metab. 2002 Dec;22(12):1440-52. Abstract

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