ACRIN-PA 4004 study: Comparison of [F-18] flutemetamol and [C-11] PiB in normal control and Alzheimer’s subjects

Objectives This single center study is designed to evaluate the performance characteristics of [18F]flutemetamol (flute) with respect to its ability to distinguish patients with clinically-diagnosed probable Alzheimer’s disease (AD) from cognitively normal elderly (NL) subjects and to independently compare its results to [11C]Pittsburgh Compound B (PiB) in the same subjects.

Methods Twenty-three subjects (15 NL (71±8.4 years old) and 8 AD (75±10.0 years old)) underwent two PET scans using either PiB or flute with >120 min between scans. ROC analysis (AUC) was used to determine whether global cortical (anterior and posterior cingulate, and frontal, parietal, lateral temporal cortex) SUVR levels distinguished AD from NL subjects. Cohort flute and PiB global SUVR measures were compared using the two-sample t test. Blinded visual reads were conducted by two experienced raters interpreting global tracer uptake on scale of 1-5. Averaged results from the raters were correlated with global SUVR measures by Pearson correlation coefficient (r).

Results Global SUVR levels produced AUC values of 0.77(95% CI: 0.54 to 1.00) for flute and 0.78(95% CI: 0.53 to 1.00) for PiB. Global SUVR levels in AD subjects trended higher than the levels found in NL subjects (P=0.042 for flute and 0.054 for PiB by t test). The average visual reads were significantly correlated with global SUVR values in all subjects (flute r=0.80, P<0.0001; PiB r=0.78, P<0.0001).

Conclusions The uptake of flute and PiB can be used to classify AD versus NL subjects. Both compounds performed similarly. AUC values increase to 0.90 and 0.89 for flute and PiB, respectively by excluding amyloid-positive NL subjects (6/15) in the ROC analyses, highlighting high specificity of flute and PiB for amyloid detection and not the diagnosis of AD. Visual reads of both compounds provided similar outcome measures indicating a close correspondence of the in vivo properties of flute and PiB.

Research Support PA CURE #410003770