Abstract Details

Title [11C]MK-6884 PET Tracer for M4 Muscarinic Cholinergic Receptors in Alzheimer’s Disease: Comparison with [18F]FDG PET

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P2 - Poster Session 2 (8:00 AM-9:00 AM)

Poster/Presentation
Number 10-008

Objective Recently, a M4 muscarinic cholinergic receptor PET tracer has been developed that shows good imaging characteristics. We report on the first group of AD patients to be studied with this tracer, [¹¹C]MK-6884.

Background Cholinergic neuron loss is a hallmark of AD. The largest class of therapeutic agents targets acetylcholinesterase in order to increase acetylcholine availability. In order to evaluate regional cholinergic tone in patients and measure target engagement for potential therapies, it would be helpful to image muscarinic receptors in vivo. Several PET 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.

Design/Methods Nine patients with Alzheimer’s disease (MMSE=15.2±5.2), aged from 60 to 76 years old (mean=68.9±5.5 years, five women), underwent [¹¹C]MK-6884 M4 receptor and [¹⁸F]FDG metabolism PET. Immediately after a bolus injection of approximately 370 MBq of [¹¹C]MK-6884, images were acquired during 90 minutes. Standardized uptake value ratios (SUVRs) were calculated between 5 to 15 minutes using the cerebellum grey matter as the reference region. [¹⁸F]FDG SUVRs were calculated following standard procedures, using the pons as the reference region.

Results As expected, [¹¹C]MK-6884 showed good 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.

Conclusions The initial experience with [¹¹C]MK-6884 suggests that this tracer may prove useful to image muscarinic receptors in AD.

Authors/Disclosures
Joseph C. Masdeu, MD, PhD, F�鶹��ýӳ�� (Houston Methodist Neurological Institute) PRESENTER	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.
Belen Pascual, PhD (Houston Methodist Hospital)	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.
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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.

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