Visual assessments of 11 C-Pittsburgh compound-B PET vs. 18 F-flutemetamol PET across the age spectrum

Visual assessments of amyloid-β PET, used for Alzheimer's disease (AD) diagnosis and treatment evaluation, require a careful approach when different PET ligands are utilized. Because the gray matter (GM) and white matter (WM) ligand bindings vary with age, the objective was to investigate the agreement between visual reads of 11 C- and 18 F-PET scans.

Cognitively unimpaired (CU) younger adults ( N  =   30; 39.5   ±   6.0   years), CU older adults ( N  =   30; 68.6   ±   5.9   years), and adults with AD ( N  =   22; 67.0   ±   8.5   years) underwent brain MRI, 11 C-Pittsburgh compound-B (PiB)-PET, and 18 F-flutemetamol-PET. Amyloid-β deposition was assessed visually by two nuclear medicine specialists on 11 C-PiB-PET and 18 F-flutemetamol-PET, and quantitatively by PET centiloids.

Seventy-two 11 C-PiB-PET and 18 F-flutemetamol-PET visual reads were concordant. However, 1 18 F-flutemetamol-PET and 9 11 C-PiB-PET were discordant with quantitative values. In four additional cases, while 11 C-PiB-PET and 18 F-flutemetamol-PET visual reads were concordant, they were discordant with quantitative values. Disagreements in CU younger adults were only with 11 C-PiB-PET visual reads. The remaining disagreements were with CU older adults.

Age, GM/WM binding, amyloid-β load, and disease severity may affect visual assessments of PET ligands. Increase in WM binding with age causes a loss of contrast between GM and WM on 11 C-PiB-PET, particularly in CU younger adults, leading to false positivity. In CU older adults, increased WM signal may bleed more into cortical regions, hiding subtle cortical uptake, especially with 18 F-flutemetamol, whereas 11 C-PiB can detect true regional positivity. Understanding these differences will improve patient care and treatment evaluation in clinic and clinical trials.