[18F]NCFHEB/[18F]Flubatine a potential PET marker of early Alzheimer`s disease
The nicotinic α4β2 acetylcholine receptor is an important target for diagnostic neuroimaging and drug development because of its involvement in learning and memory processes, neuropsychiatric diseases such as Alzheimer´s disease, Parkinsons´s disease, Tourette´s syndrome, epilepsy, autism, attention-deficit hyperactivity disorder, schizophrenia, and depression, as well as drug addiction and pain. In our group, highly affine and selective α4β2 nAChR targeting radiotracers have been developed which are related to the structure of the alkaloid epibatidine. The two radiolabeled enantiomers of norchloro-fluoro-homoepibatidine (NCFHEB), (+)-[18F]flubatine and (-)-[18F]flubatine, were investigated in piglets in dynamic PET studies. (-)-[18F]flubatine proofed to possess radiotracer properties superior to the clinically used 2-[18F]F-A85380, and was already assessed in man to quantitatively image α4β2nAChR in the living brain. The other enantiomer (+)-[18F]flubatine is currently also under investigation in patients with Alzheimer´s disease.
Accumulating evidence also indicates a role for nAChRs in carcinogenesis. Further studies are needed to prove the suitability of [18F]flubatine for tumor imaging.
|PET images (maximum intensity projection, MIP) 1h p.i. of a (A) mouse (29.7 g), (B) piglet (14.0 kg) and (C) human (77 kg) after injection of [18F]flubatine. The accumulation in the brain, liver, urinary bladder, red marrow and the intestines can be clearly identified in all three species. Compared with humans there is an additional tracer uptake in the salivary gland in mice and in the eyes in piglets.|
Department of Nuclear Medicine and Department of Psychiatry, University of Leipzig
Central Institute for Electronics, Research Center Juelich
Advanced Biochemical Compounds ABX GmbH, Radeberg
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Financial support by
- Deutsche Forschungsgemeinschaft - DFG
- Federal Ministry of Education and Research
- Helmholtz Validation Fonds