3-(Benzyloxy)-1-(5-[ 18 F]fluoropentyl)-5-nitro-1H-indazole: a PET radiotracer to measure acetylcholinesterase in brain.

AIM: Noninvasive studies of the acetylcholinesterase (AChE) level in Alzheimer's disease (AD) patients can contribute to a better understanding of the disease and its therapeutic. We propose 3-(benzyloxy)-1-(5-[18 F]fluoropentyl)-5-nitro-1H-indazole, [18 F]-IND1, structurally related to the AChE-inhibitor CP126,998, as a new positron emission tomography-radiotracer.

EXPERIMENTAL: Radiosynthesis, with 18F, stability, lipophilicity and protein binding of [18F]-IND1 were studied. In vivo behavior, in normal mice and on AD mice models, were also analyzed.

RESULTS: [18 F]-IND1 was obtained in good radiochemical yield, was stable for at least 2 h in different conditions, and had adequate lipophilicity for blood-brain barrier penetration. Biodistribution studies, in normal mice, showed that [18 F]-IND1 was retained in the brain after 1 h. In vivo tacrine-blocking experiments indicated this uptake could be specifically due to AChE interaction. Studies in transgenic AD mice showed differential, compared with normal mice, binding in many brain regions.

CONCLUSION: [18 F]-IND1 can be used to detect AChE changes in AD patients.