BACKGROUND: Carbon-11-labelled Pittsburgh compound B ((11)C-PiB) PET is a marker 
of cortical fibrillar amyloid-beta load in vivo. We used (11)C-PiB PET to 
investigate whether bapineuzumab, a humanised anti-amyloid-beta monoclonal 
antibody, would reduce cortical fibrillar amyloid-beta load in patients with 
Alzheimer's disease.
METHODS: Patients with mild-to-moderate Alzheimer's disease were randomly 
assigned to receive intravenous bapineuzumab or placebo in a ratio of seven to 
three in three ascending dose groups (0.5, 1.0, or 2.0 mg/kg). Each dose group 
was enrolled after safety review of the previous group. Randomisation was by 
interactive voice response system; masking was achieved with numbered kit 
allocation. Patients, investigators, study site personnel, sponsor staff, and 
carers were masked to treatment. Patients received up to six infusions, 13 weeks 
apart, and had (11)C-PiB PET scans at baseline and at weeks 20, 45, and 78. The 
primary outcome was the difference between the pooled bapineuzumab group and the 
pooled placebo group in mean change from screening to week 78 in (11)C-PiB 
cortical to cerebellar retention ratio averaged across six cortical regions of 
interest. Analysis was by modified intention to treat. This study is registered 
with EudraCT, number 2004-004120-12; ISRCTN17517446.
FINDINGS: 28 patients were assigned to bapineuzumab (n=20) or placebo (n=8). 19 
patients in the bapineuzumab group and seven in the placebo group were included 
in the modified intention-to-treat analysis. Estimated mean (11)C-PiB retention 
ratio change from baseline to week 78 was -0.09 (95% CI -0.16 to -0.02; p=0.014) 
in the bapineuzumab group and 0.15 (95% CI 0.02 to 0.28; p=0.022) in the placebo 
group. Estimated mean difference in (11)C-PiB retention ratio change from 
baseline to week 78 between the bapineuzumab group and the placebo group was 
-0.24 (95% CI -0.39 to -0.09; p=0.003). Differences between the bapineuzumab 
group and the placebo group in the individual regions of interest were similar 
to the overall mean difference. Adverse events were typically mild to moderate 
in severity and transient. Two patients in the 2.0 mg/kg bapineuzumab group had 
transient cerebral vasogenic oedema.
INTERPRETATION: Treatment with bapineuzumab for 78 weeks reduced cortical 
(11)C-PiB retention compared with both baseline and placebo. (11)C-PiB PET seems 
to be useful in assessing the effects of potential Alzheimer's disease 
treatments on cortical fibrillar amyloid-beta load in vivo.
FUNDING: Elan Pharmaceuticals and Wyeth Research.