In vitro binding of [3H]CUMI-101, a HT1AR radioligand in Alzheimer’s disease

Objectives Serotonin1A receptors (5-HT1AR) have been implicated in the pathophysiology of neuropsychiatric and neurodegenerative disorders including Alzheimer’s disease. We have recently evaluated [11C]CUMI-101 as a 5-HT1AR radioligand based on in vivo studies in baboons and human subjects and [3H]CUMI-101 in vitro by quantitative autoradiography studies in postmortem baboon and human brain sections. In this study, we have evaluated the ability of [3H]CUMI-101 binding in postmortem brain sections of Alzheimer’s disease in comparison to control subjects.

Methods The [3H]CUMI-101 was obtained from NIMH chemical synthesis and drug supply program. The in vitro autoradiography studies of [3H]CUMI-101 were performed in postmortem brain sections (20 μm) containing 2 nM of [3H]CUMI-101 (specific activity 77.7 Ci/mmol) for 60 min at 37oC. Adjacent sections were incubated with [3H]CUMI-101 and 1µm WAY100,635 to determine specific binding to 5-HT1ARs. Slides were exposed to tritium-sensitive screen and developed using Kodak D-19 developer. The autoradiograms were sampled using a computer-based image analysis system MCID.

Results 101 was found in the prefrontal cortex of Alzheimer’s disease in comparison to control. These findings are in excellent agreement with previously reported autoradiography studies.

Conclusions Our studies demonstrated a down regulation of 5-HT1AR in Alzheimer’s disease brain. These studies suggest that [11C]CUMI-101 can be a potential tracer for the in vivo imaging of Alzheimer’s disease with PET.