Objective: To characterize the M2 muscarinic acetylcholine receptor binding in patients with cervical dystonia, measured with non-invasive high-resolution PET, using [18F]FP-TZTP ligand.

Background: While antimuscarinic medications are useful in the symptomatic treatment of dystonia, the role of muscarinic acetylcholine neurotransmission remains unclear [1]. Abnormalities in cholinergic neurotransmission have been identified in animal models and humans with dystonia [2-4] . [18F]FP-TZTP is a radiopharmaceutical ligand used in PET imaging that selectively and reversibly binds to the M2 muscarinic receptors [5]. A non-invasive estimation of normalized distribution volume (VT*) has been validated for  [¹⁸F]FP-TZTP PET [6]. This novel ligand and non-invasive technique can be useful for studying acetylcholine receptor binding in cervical dystonia patients.

Method: M2 muscarinic acetylcholine receptor mapping was performed in 10 patients with cervical dystonia (mean age 56 years old, SD=13, 5 females) and 13 healthy volunteers (mean age 57 years old, SD=13, 7 females), with [¹⁸F]FP-TZTP PET using non- invasive high resolution research tomography. A two-parameter multilinear reference tissue model (MRTM2) was used to generate parametric images of VT*[6]. Average VT* for the whole brain was extracted for each subject and compared between groups. Regional analysis of tracer binding is ongoing.

Results: [¹⁸F]FP-TZTP PET imaging with the MRTM2 model provided a map of M2 muscarinic acetylcholine receptors in the brain of each participant. Between group comparisons with age as a covariate, showed a significant difference of the group means for the whole brain VT* value (p<0.05).

Conclusion: [¹⁸F]FP-TZTP PET can be a potential non-invasive tool for assessment of M2 cholinergic receptor binding in cervical dystonia which can provide insight into its pathophysiology.

References: 1. Eskow Jaunarajs, K.L., et al., Striatal cholinergic dysfunction as a unifying theme in the pathophysiology of dystonia. Prog Neurobiol, 2015. 127-128: p. 91-107.
2. Mazere, J., et al., Striatal and cerebellar vesicular acetylcholine transporter expression is disrupted in human DYT1 dystonia. Brain, 2021.
3. Sciamanna, G., et al., Cholinergic dysregulation produced by selective inactivation of the dystonia-associated protein torsinA. Neurobiol Dis, 2012. 47(3): p. 416-27.
4. Pappas, S.S., et al., Forebrain deletion of the dystonia protein torsinA causes dystonic-like movements and loss of striatal cholinergic neurons. Elife, 2015. 4: p. e08352.
5. Podruchny, T.A., et al., In vivo muscarinic 2 receptor imaging in cognitively normal young and older volunteers. Synapse, 2003. 48(1): p. 39-44.
6. Ichise, M., R.M. Cohen, and R.E. Carson, Noninvasive estimation of normalized distribution volume: application to the muscarinic-2 ligand [(18)F]FP-TZTP. J Cereb Blood Flow Metab, 2008. 28(2): p. 420-30.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/muscarinic-m2-cholinergic-receptors-in-cervical-dystonia/