Introduction to [11C]PIB

Pittsburgh Compound B (PIB, PiB, or 6-OH-BTA-1) is a derivative of thioflavin T, and both bind to amyloid-β; [11C]PIB has been successfully used as a PET ligand to in vivo visualization and quantification of amyloid-β deposits.

Analysis of [11C]PIB PET studies

[11C]PIB binding to amyloid-β in the grey brain matter is specific and reversible. [11C]PIB binding in white matter is non-specific and non-saturable (Fodero-Tavoletti et al., 2009), but due to slower kinetics the uptake is prominent at later time points, which may impede the quantification of amyloid-β deposits in the grey matter in case of considerable partial volume effect.

The recommended analysis methods for quantification of amyloid load in the brain are

Logan plot with PIB

Distribution volume ratio (DVR), or binding potential (BPND = DVR-1), can be calculated with Logan plot without arterial plasma data sampling, using cerebellar cortex as input (Mintun et al. 2006; Li et al. 2008). Reference region k2 was set to 0.2 min-1, but this value had only minimal impact on the results (Mintun et al. 2006). However, it may advance the time when Logan plot reaches linearity, thus reducing the required total scan length.

Regional analysis

Estimate the regional DVR using logan with option -k2=0.2 and set fit time from 20 minutes to a common end time.

Pixel-by-pixel analysis

To produce DVR images use imgdv with option -k2=0.2 and set fit start time to 20. BPND images (Mikhno et al., 2008) can be achieved by subtracting 1 from DVR images.

Tissue-to-cerebellum ratio

Amyloid load can be quantified by computing region-to-cerebellum ratio over 60 to 90 minutes (Lopresti et al., 2005; Kemppainen et al. 2006), either regionally withdftratio or pixel-by-pixel withimgratio. Optimal time range was thoroughly studied by McNamee et al. (2009); their suggestion was to use 40-60-min period in studies limited by low injected dose, but otherwise the 50-70-min period because of greater measurement stability, especially for longitudinal multisite studies.

Advantages of the ratio approach are 1) large effect sizes for Alzheimer's Disease (AD) and control group differences (Lopresti et al., 2005), and 2) possibility to obtain the required data from a single relatively short scan.

AD patients may have also cerebellar plaques, which may render cerebellum vulnerable as a reference area. Therefore, it may be necessary to calculated results also by using pons as a reference area (Koivunen et al., 2008).


References:

Fodero-Tavoletti MT, Rowe CC, McLean CA, Leone L, Li Q-X, Masters CL, Cappai R, Villemagne VL. Characterization of PiB binding to white matter in Alzheimer disease and other dementias. J Nucl Med. 2009; 50: 198-204.

Kemppainen NM, Aalto S, Wilson IA, Någren K, Helin S, Brück A, Oikonen V, Kailajärvi M, Scheinin M, Viitanen M, Parkkola R, Rinne JO. Voxel-based analysis of PET amyloid ligand [11C]PIB uptake in Alzheimer disease. Neurology 2006; 67(9): 1575-1580.

Kemppainen NM, Aalto S, Karrasch M, Någren K, Savisto N, Oikonen V, Viitanen M, Parkkola R, Rinne JO. Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild AD. Ann Neurol. 2008; 63(1): 112-118.

Koivunen J, Verkkoniemi A, Aalto S, Paetau A, Ahonen JP, Viitanen M, Någren K, Rokka J, Haaparanta M, Kalimo H, Rinne JO. PET amyloid ligand [11C]PIB uptake shows predominantly striatal increase in variant Alzheimer's disease. Brain 2008; 131(7): 1845-1853.

Li Y, Rinne JO, Mosconi L, Pirraglia E, Rusinek H, DeSanti S, Kemppainen N, Någren K, Kim B-C, Tsui W, de Leion MJ. Regional analysis of FDG and PIB-PET images in normal aging, mild cognitive impairment, and Alzheimer’s disease. Eur J Nucl Med Mol Imaging 2008; 35: 2169–2181.

Lopresti BJ, Klunk WE, Mathis CA, Hoge JA, Ziolko SK, Lu X, Meltzer CC, Schimmel K, Tsopelas ND, DeKosky ST, Price JC. Simplified quantification of Pittsburgh compound B amyloid imaging PET studies: a comparative analysis. J Nucl Med. 2005; 46(12): 1959-1972.

McNamee RL, Yee SH, Price JC, Klunk WE, Rosario B, Weissfeld L, Ziolko S, Berginc M, Lopresti B, Dekosky S, Mathis CA. Consideration of optimal time window for Pittsburgh Compound B PET summed uptake measurements. J Nucl Med. 2009; 50(3): 348-355.

Mikhno A, Devanand D, Pelton G, Cuasay K, Gunn R, Upton N, Lai RY, Libri V, Mann JJ, Parsey RV. Voxel-based analysis of 11C-PIB scans for diagnosing Alzheimer's Disease. J Nucl Med. 2008; 49: 1262-1269.

Mintun MA, LaRossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, Klunk WE, Mathis CA, DeKosky ST, Morris JC. [11C]PIB in a nondemented population: Potential antecedent marker of Alzheimer disease. Neurology 2006; 67: 446-452.

Scheinin NM, Tolvanen TK, Wilson IA, Arponen EM, Någren KA, Rinne JO. Biodistribution and Radiation Dosimetry of the Amyloid Imaging Agent 11C-PIB in Humans. J Nucl Med. 2007; 48(1): 128-133.

Ziolko SK, Weissfeld LA, Klunk WE, Mathis CA, Hoge JA, Lopresti BJ, DeKosky ST, Price JC. Evaluation of voxel-based methods for the statistical analysis of PIB PET amyloid imaging studies in Alzheimer's disease. Neuroimage 2006; 33: 94-102.



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