3-(Benzyloxy)-1-(5-[18F]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-[18F]fluoropentyl)-5-nitro-1H-indazole, [18F]-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
[18F]-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 [18F]-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
[18F]-IND1 can be used to detect AChE changes in AD patients.
['Fernández|Soledad|S|', 'Giglio|Javier|J|', 'Reyes|Ana Laura|AL|', 'Damián|Andrés|A|', 'Pérez|Concepción|C|', 'Pérez|Daniel I|DI|', 'González|Mercedes|M|', 'Oliver|Patricia|P|', 'Rey|Ana|A|', 'Engler|Henry|H|', 'Cerecetto|Hugo|H|']
D000110:Acetylcholinesterase D000544:Alzheimer Disease D000818:Animals D001921:Brain D005260:Female D006801:Humans D007191:Indazoles D051379:Mice D015394:Molecular Structure D049268:Positron-Emission Tomography D014018:Tissue Distribution
PET acetylcholinesterase brain Alzheimer's disease 18F indazole