Comparison of <sup>11</sup>C-Pittsburgh Compound B and <sup>18</sup>F-Flutemetamol White Matter Binding in PET
Burcu Zeydan, Christopher G. Schwarz, Scott A. Przybelski, Timothy G. Lesnick, Walter K. Kremers, Matthew L. Senjem, Orhun H. Kantarci, Hoon‐Ki Min, Bradley J. Kemp, Clifford R. Jack, Kejal Kantarci, Val J. Lowe
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 “<sup>11</sup>C-Pittsburgh compound-B” (<sup>11</sup>C-PiB) have been considered for quantitative measurement of myelin content changes in multiple sclerosis (MS), but <sup>11</sup>C-PiB is not commercially available given its short half-life. A “<sup>18</sup>F-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. <b>Methods:</b> Cognitively unimpaired (CU) older and younger adults (<i>N</i> = 61) were recruited from the community responding to a study advertisement for β-amyloid PET. Participants prospectively underwent MRI, <sup>11</sup>C-PiB and <sup>18</sup>F-Flutemetamol PET scans. MRI-FLAIR images were segmented into WMH and NAWM and registered to the T1-weighted MRI. <sup>11</sup>C-PiB and <sup>18</sup>F-Flutemetamol PET images were also registered to the T1-weighted image MRI. <sup>11</sup>C-PiB and <sup>18</sup>F-Flutemetamol standard uptake value ratios (SUVrs) from the WMH and NAWM were calculated using cerebellar crus uptake as a reference for both <sup>11</sup>C-PiB and <sup>18</sup>F-Flutemetamol. <b>Results:</b> Median age was 38 years (range 30-48) in younger adults and 67 years (range 61-83) in older adults. WMH and NAWM SUVrs were higher with <sup>18</sup>F-Flutemetamol than <sup>11</sup>C-PiB both in older (p<0.001) and in younger (p<0.001) CU adults. <sup>11</sup>C-PiB and <sup>18</sup>F-Flutemetamol SUVrs were higher in older compared to younger CU adults in both WMH (p<0.001) and in NAWM (p<0.001). <sup>11</sup>C-PiB and <sup>18</sup>F-Flutemetamol SUVrs were higher in NAWM compared to WMH in both older (p<0.001) and in younger (p<0.001) CU adults. There was no apparent difference between <sup>11</sup>C-PiB versus <sup>18</sup>F-Flutemetamol SUVrs in differentiating WMH from NAWM in older and in younger adults. <b>Conclusion:</b><sup>11</sup>C-PiB and <sup>18</sup>F-Flutemetamol show a similar topographical pattern of uptake in white matter with a similar association with age in WMH and NAWM. <sup>11</sup>C-PiB and <sup>18</sup>F-Flutemetamol can also effectively distinguish between WMH and NAWM. However, given its longer half-life, commercial availability, and higher binding potential, <sup>18</sup>F-Flutemetamol can be an alternative to <sup>11</sup>C-PiB in molecular imaging studies specifically targeting MS to evaluate white matter integrity.