Comparison of (11)C-Pittsburgh Compound B and (18)F-Flutemetamol White Matter Binding in PET.

PET imaging with β-amyloid ligands is emerging as a molecular imaging technique targeting white matter integrity and demyelination. β-amyloid PET ligands such as 11C-Pittsburgh compound B (11C-PiB) have been considered for quantitative measurement of myelin content changes in multiple sclerosis, but 11C-PiB is not commercially available given its short half-life. A 18F PET ligand such as flutemetamol with a longer half-life may be an alternative, but its ability to differentiate white matter hyperintensities (WMH) from normal-appearing white matter (NAWM) and its relationship with age remains to be investigated. Methods: Cognitively unimpaired (CU) older and younger adults (n = 61) were recruited from the community responding to a study advertisement for β-amyloid PET. Participants prospectively underwent MRI, 11C-PiB, and 18F-flutemetamol PET scans. MRI fluid-attenuated inversion recovery images were segmented into WMH and NAWM and registered to the T1-weighted MRI. 11C-PiB and 18F-flutemetamol PET images were also registered to the T1-weighted MRI. 11C-PiB and 18F-flutemetamol SUV ratios (SUVrs) from the WMH and NAWM were calculated using cerebellar crus uptake as a reference for both 11C-PiB and 18F-flutemetamol. Results: The median age was 38 y (range, 30-48 y) in younger adults and 67 y (range, 61-83 y) in older adults. WMH and NAWM SUVrs were higher with 18F-flutemetamol than with 11C-PiB in both older (P < 0.001) and younger (P < 0.001) CU adults. 11C-PiB and 18F-flutemetamol SUVrs were higher in older than in younger CU adults in both WMH (P < 0.001) and NAWM (P < 0.001). 11C-PiB and 18F-flutemetamol SUVrs were higher in NAWM than WMH in both older (P < 0.001) and younger (P < 0.001) CU adults. There was no apparent difference between 11C-PiB and 18F-flutemetamol SUVrs in differentiating WMH from NAWM in older and in younger adults. Conclusion:11C-PiB and 18F-flutemetamol show a similar topographic pattern of uptake in white matter with a similar association with age in WMH and NAWM. 11C-PiB and 18F-flutemetamol can also effectively distinguish between WMH and NAWM. However, given its longer half-life, commercial availability, and higher binding potential, 18F-flutemetamol can be an alternative to 11C-PiB in molecular imaging studies specifically targeting multiple sclerosis to evaluate white matter integrity.

Zeydan B ，Schwarz CG ，Przybelski SA ，Lesnick TG ，Kremers WK ，Senjem ML ，Kantarci OH ，Min PH ，Kemp BJ ，Jack CR Jr ，Kantarci K ，Lowe VJ ... -  《-》

Reduced binding of Pittsburgh Compound-B in areas of white matter hyperintensities.

Goodheart AE ，Tamburo E ，Minhas D ，Aizenstein HJ ，McDade E ，Snitz BE ，Price JC ，Mathis CA ，Lopez OL ，Klunk WE ，Cohen AD ... -  《-》

Comparison of qualitative and quantitative imaging characteristics of [11C]PiB and [18F]flutemetamol in normal control and Alzheimer's subjects.

Mountz JM ，Laymon CM ，Cohen AD ，Zhang Z ，Price JC ，Boudhar S ，McDade E ，Aizenstein HJ ，Klunk WE ，Mathis CA ... -  《NeuroImage-Clinical》

Comparison of [(18)F]Flutemetamol and [(11)C]Pittsburgh Compound-B in cognitively normal young, cognitively normal elderly, and Alzheimer's disease dementia individuals.

Lowe VJ ，Lundt E ，Knopman D ，Senjem ML ，Gunter JL ，Schwarz CG ，Kemp BJ ，Jack CR Jr ，Petersen RC ... -  《NeuroImage-Clinical》

White Matter Reference Region in PET Studies of (11)C-Pittsburgh Compound B Uptake: Effects of Age and Amyloid-β Deposition.

Amyloid-β (Aβ) deposition as seen on PET using an Aβ-binding agent is a critical diagnostic biomarker for Alzheimer disease (AD). Some reports suggest using white matter (WM) as a reference region for quantification of serial Aβ PET studies; however, nonspecific WM retention in Aβ PET in people with dementia or cognitively unimpaired (CU) has been widely reported and is poorly understood. Methods: To investigate the suitability of WM as a reference region and the factors affecting WM 11C-Pittsburgh compound B (11C-PiB) uptake variability, we conducted a retrospective study on 2 large datasets: a longitudinal study of participants (n = 577) who were CU, had mild cognitive impairment, or had dementia likely due to AD; and a cross-sectional study of single-scan PET imaging in CU subjects (n = 1,349). In the longitudinal study, annual changes in WM 11C-PiB uptake were assessed, and in the cross-sectional study, WM 11C-PiB uptake was assessed relative to subject age. Results: Overall, we found that WM 11C-PiB uptake showed age-related increases, which varied with the WM regions selected. Further, variable annual WM 11C-PiB uptake changes were seen with different gray matter (GM) 11C-PiB baseline uptake levels. Conclusion: WM binding increases with age and varies with GM 11C-PiB. These correlations should be considered when using WM for normalization in 11C-PiB PET studies. The cerebellar crus1+crus2 showed no increase with age and cerebellar GM+WM showed minimal increase, supporting their use as reference regions for cross-sectional studies comparing wide age spans. In longitudinal studies, the increase in WM uptake may be minimal in the short-term and thus using WM as a reference region in these studies seems reasonable. However, as participants age, the findings may be affected by changes in WM uptake. Changes in WM 11C-PiB uptake may relate to disease progression, warranting examination of the causes of WM 11C-PiB uptake.

Lowe VJ ，Lundt ES ，Senjem ML ，Schwarz CG ，Min HK ，Przybelski SA ，Kantarci K ，Knopman D ，Petersen RC ，Jack CR Jr ... -  《-》