18F‐flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: A phase 2 trial

Abstract

Objective The most widely studied positron emission tomography ligand for in vivo β-amyloid imaging is ¹¹C-Pittsburgh compound B (¹¹C-PIB). Its availability, however, is limited by the need for an on-site cyclotron. Validation of the ¹⁸F-labeled PIB derivative ¹⁸F-flutemetamol could significantly enhance access to this novel technology. Methods Twenty-seven patients with early-stage clinically probable Alzheimer disease (AD), 20 with amnestic mild cognitive impairment (MCI), and 15 cognitively intact healthy volunteers (HVs) above and 10 HVs below 55 years of age participated. The primary endpoint was the efficacy of blinded visual assessments of ¹⁸F-flutemetamol scans in assigning subjects to a raised versus normal uptake category, with clinical diagnosis as the standard of truth (SOT). As secondary objectives, we determined the correlation between the regional standardized uptake value ratios (SUVRs) for ¹⁸F-flutemetamol and its parent molecule ¹¹C-PIB in 20 of the AD subjects and 20 of the MCI patients. We also determined test-retest variability of ¹⁸F-flutemetamol SUVRs in 5 of the AD subjects. Results Blinded visual assessments of ¹⁸F-flutemetamol scans assigned 25 of 27 scans from AD subjects and 1 of 15 scans from the elderly HVs to the raised category, corresponding to a sensitivity of 93.1% and a specificity of 93.3% against the SOT. Correlation coefficients between cortical ¹⁸F-flutemetamol SUVRs and ¹¹C-PIB SUVRs ranged from 0.89 to 0.92. Test-retest variabilities of regional SUVRs were 1 to 4%. Interpretation ¹⁸F-Flutemetamol performs similarly to the ¹¹C-PIB parent molecule within the same subjects and provides high test-retest replicability and potentially much wider accessibility for clinical and research use. ANN NEUROL 2010