Title: Low Retention of [S-methyl-11C]MeS-IMPY to β-amyloid Plaques in Patients with Alzheimers Disease
Volume: 2
Issue: 2
Author(s): Nicholas Seneca, Lisheng Cai, Jeih-San Liow, Sami S. Zoghbi, Robert Gladding, John T. Little, Paul S. Aisen, Jinsoo Hong, Victor W. Pike and Robert B. Innis
Affiliation:
Keywords:
Positron emission tomography, β-amyloid, [11C]MeS-IMPY, Alzheimer's disease
Abstract: Alzheimers disease (AD) is characterized pathologically by the accumulation of β-amyloid plaques in brain. We developed a novel positron emission tomographic (PET) radioligand, [11C]MeS-IMPY ([S-methyl-11C]N,N-dimethyl- 4-(6-(methylthio)imidazo[1,2-a]pyridine-2-yl)aniline). The objective of this study was to determine if [11C]MeS-IMPY can detect β-amyloid plaques in patients with AD. Ten subjects (4 patients with AD and 6 healthy controls) had PET scans of 90 min as well as serial sampling of arterial plasma. Total distribution volume was calculated from radioactivity in brain and concentrations of radioligand in arterial plasma. After injection of [11C]MeS-IMPY in both groups, peak brain uptake was high (∼ 450% SUV), peaked early at ∼ 2 min and washed out quickly. The time-course of brain radioactivity in all regions was virtually identical in AD patients and healthy controls. Although distribution volume of neocortical regions was ∼ 26% higher in AD patients than in controls, the differences were statistically insignificant (P = 0.143). In addition, distribution volume in all regions and in both groups increased during the entire scan, which is consistent with the accumulation of radiometabolite(s) in brain. The rapid washout of [11C]MeS-IMPY from brain may have been caused by inadequate binding affinity, and the small differences between patients and healthy subjects were likely caused, in part, by the accumulation of radiometabolite(s) in brain. We conclude that [11C]MeS-IMPY is able to image β-amyloid in brains of patients with AD, but that chemical analogs with higher affinity and non-problematic radiometabolites will be more useful imaging agents.
