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

Introduction Neuritic amyloid plaques and neurofibrillary tangles, the hallmark pathologic lesions of Alzheimer's disease, are thought to develop before the symptoms of brain failure are clinically detectable. Imaging methods capable of detecting the presence of neuritic amyloid plaques should improve a clinician's ability to identify Alzheimer's disease during the earliest symptomatic phase and to identify at-risk individuals presymptomatically. Currently the best studied amyloid imaging ligand is [¹¹C]Pittsburgh Compound B ([¹¹C]PiB). However, the 20-minute half-life of this radiotracer limits its use. This study is designed to evaluate the performance characteristics of [¹⁸F]flutemetamol and to independently compare results to [¹¹C]PiB in the same subjects. Methods Twenty-three subjects, 15 cognitively normal (NL) and 8 with a clinical diagnosis of Alzheimer's Dementia (AD), underwent [¹¹C]PiB and [¹⁸F]flutemetamol PET scans within 28 days of study enrollment. We studied both normal and AD subjects to assess the uptake characteristics across a range of amyloid positivity. Blinded visual reads were conducted by five raters. Correlation analyses were performed between cortical SUVR for the two tracers and also between rater scores and SUVR for each tracer. Overall reader accuracy for classifying scans as amyloid positive or negative was determined for each tracer using SUVR classification as the standard. Results The linear correlation coefficient between global cortical SUVR for the two tracers was R² = 0.85, indicating that both tracers have similar retention characteristics. The two tracers were well correlated for rater-determined AD-like positivity (Cohen κ = 0.82). Averaged visual ratings and global cortical SUVR disagreed on their classification in 2/23 [¹¹C]PiB scans and 4/23 [¹⁸F]flutemetamol scans. Conclusions [¹¹C]PiB and [¹⁸F]flutemetamol have similar retention characteristics across a range of amyloid negative to positive subjects. Both tracers performed similarly when a standardized visual read technique was used to classify scans as amyloid-positive or amyloid-negative and correlated well with SUVR classifications. However, care in visual interpretation of amyloid positive versus amyloid negative regions should be taken, particularly in the case of [¹⁸F]flutemetamol when considering cortical vs. white-matter retention.