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Abstract Details

[11C]MK-6884 PET Tracer for M4 Muscarinic Cholinergic Receptors in Alzheimer’s Disease: Comparison with [18F]FDG PET
Aging, Dementia, and Behavioral Neurology
Aging and Dementia Posters (7:00 AM-5:00 PM)
043

To report on the first group of AD patients studied with a new M4 muscarinic cholinergic receptor PET tracer, [11C]MK-6884.

Cholinergic neuron loss is a hallmark of AD. The largest class of therapeutic agents for AD targets acetylcholinesterase in order to increase acetylcholine availability. To evaluate regional cholinergic tone in individual patients and measure target engagement for potential therapies, it would be helpful to image muscarinic receptors in vivo. Several imaging tracers have been developed to image cholinergic receptors, but the findings with these agents have been either negative or too subtle to be of use. Recently, a M4 muscarinic cholinergic receptor PET tracer has been developed, [11C]MK-6884, which shows good imaging characteristics.

Nine patients with Alzheimer’s disease (MMSE=15.2±5.2, mean age=68.9±5.5 years, five women), underwent [11C]MK-6884 M4 receptor and [18F]FDG metabolism PET. M4 images were acquired during 90 minutes after a bolus injection of 370 MBq of [11C]MK-6884. Standardized uptake value ratios (SUVRs) were calculated using the cerebellum grey matter as the reference region. [18F]FDG SUVRs were calculated following standard procedures, using the cerebellum grey matter as the reference region. 

As expected, [11C]MK-6884 showed a high uptake in the basal ganglia, with low values in thalamus. Cortical uptake was reduced mostly in parieto-temporal association cortex, corresponding well with the clinical syndrome: patients with a predominant language problem had greater loss in the left hemisphere and the opposite was true for those with visuospatial skills impairment. Frontal lobes were also affected, but not as much as the posterior structures. There was a concordance in cortical [11C]MK-6884 and [18F]FDG PET values, indicating that the [11C]MK-6884 binding was disease specific, but also discordant areas, highlighting the potential specificity of [11C]MK-6884. 

The initial experience with [11C]MK-6884 suggests that this tracer may prove useful to image muscarinic receptors in AD.
Authors/Disclosures
Belen Pascual, PhD (Houston Methodist Hospital)
PRESENTER 		The institution of Prof. Pascual has received research support from NIH. The institution of Prof. Pascual has received research support from NIH.
Paolo Zanotti Fregonara Paolo Zanotti Fregonara has nothing to disclose.
Meixiang Yu No disclosure on file
Quentin Funk Quentin Funk has nothing to disclose.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Anthony S. Basile, PhD (Merck Research Laboratories) Dr. Basile has received personal compensation for serving as an employee of Merck Research Labs. Dr. Basile has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Above and Beyond Research. Dr. Basile has received stock or an ownership interest from Merck Research Labs. Dr. Basile has received intellectual property interests from a discovery or technology relating to health care.
Joseph C. Masdeu, MD, PhD, FÂ鶹´«Ã½Ó³»­ (Houston Methodist Neurological Institute) Dr. Masdeu has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Lilly . The institution of Dr. Masdeu has received research support from NIH. The institution of Dr. Masdeu has received research support from Houston Methodist Foundation. The institution of Dr. Masdeu has received research support from Alector. The institution of Dr. Masdeu has received research support from Aviado-Bio. Dr. Masdeu has received publishing royalties from a publication relating to health care. Dr. Masdeu has received publishing royalties from a publication relating to health care. Dr. Masdeu has received personal compensation in the range of $100,000-$499,999 for serving as a Director, Nantz Nal Alzheimer Center with HOUSTON METHODIST NEUROLOGICAL INSTITUTE.