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

Abstract

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.

Keywords: 11C-Pittsburgh compound B; 18F-flutemetamol; PET; normal appearing white matter; white matter hyperintensity.