New Tracer for Nicotinic Receptors Promises Improved Specificity

Researchers at NIDA's Intramural Research Program have developed a radiolabeled compound for animal studies of nicotinic acetylcholine receptors in the brain. Tests in monkeys indicate that the new tracer readily enters the animals' brains and binds primarily to the nicotinic receptor subtype called α4β2*. These receptors play a role in nicotine addiction and have been implicated in other neurological conditions, including dementia, epilepsy, depression, and anxiety.

In brain regions containing these receptors, the new radiotracer's accumulation is greater than that of 2FA, the tracer currently used in human imaging studies. As a result, the new tracer produces sharper and more detailed positron emission tomography images and may be especially useful for studying α4β2* nicotinic receptors in brain areas where they are sparsely distributed. The specificity of the new radiotracer accumulation for the regions with these receptors is three- to four-fold that of 2FA, and tests in mice indicate that the new compound is equally safe, says Dr. Alexey G. Mukhin, now at Duke University in Durham, North Carolina.

If further animal and human imaging research confirms these results, the tracer could advance the study of the relationships between α4β2* receptors and specific aspects of nicotine addiction and promote the development of medications for a wide variety of disorders. The chemical name for the new tracer is 6-chloro-3-((2-(S)-azetidinyl)methoxy)-5-(2-fluoropyridin-4-yl)pyridine ([18F]NIDA522131).

Journal of Neurochemistry 104(2):306-315, 2008. [Abstract]