{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:28:48Z","timestamp":1785421728175,"version":"3.56.0"},"reference-count":39,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["(Ricerca Corrente) - no specific number"],"award-info":[{"award-number":["(Ricerca Corrente) - no specific number"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"award":["(Ricerca Corrente) - no specific number"],"award-info":[{"award-number":["(Ricerca Corrente) - no specific number"]}],"id":[{"id":"https:\/\/ror.org\/00789fa95","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Positron emission tomography (PET) of muscarinic acetylcholine receptors has evolved from a receptor-mapping exercise into a potential translational tool for probing cholinergic dysfunction in neurodegenerative disease. However, the field still lacks a clear hierarchy of clinical value across receptor subtypes, tracers, and quantitative analysis strategies, including acquisition protocols and kinetic modeling approaches. In the M2 arena, [18F]FP-TZTP has been associated with higher distribution volumes in older APOE-\u03b54 carriers, but the biological meaning of this signal remains uncertain in the absence of longitudinal conversion data and with quantification approaches that are difficult to implement routinely. Among M4 ligands, [11C]MK-6884 is the most advanced and reproducible tracer to date, yet its clinical evidence still rests on proof-of-concept studies, mainly in moderate-to-severe Alzheimer\u2019s disease, with important methodological limitations. In our view, muscarinic PET should now be reframed less as a stand-alone diagnostic biomarker and more as a platform for mechanistic and pharmacodynamic studies, especially for the development and monitoring of muscarinic-positive allosteric modulators. Future progress will depend on longitudinal multicenter validation, simplified quantification pipelines, and next-generation PET systems capable of capturing tracer kinetics more efficiently.<\/jats:p>","DOI":"10.3390\/medsci14030341","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T18:35:05Z","timestamp":1782239705000},"page":"341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Muscarinic Receptor PET in Neurodegeneration: Promise, Pitfalls, and Translational Priorities"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4423-5496","authenticated-orcid":false,"given":"Luca","family":"Filippi","sequence":"first","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome \u2018Tor Vergata\u2019, Via Montpellier 1, 00133 Rome, Italy"},{"name":"Nuclear Medicine Research Unit, IRCCS San Raffaele Roma, Via della Pisana 235, 00163 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5172-1508","authenticated-orcid":false,"given":"Roberta","family":"Danieli","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Research Unit, IRCCS San Raffaele Roma, Via della Pisana 235, 00163 Rome, Italy"},{"name":"Department of Human Sciences and Promotion of the Quality of Life, University San Raffaele, Via di Val Cannuta 247, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/7854_2020_141","article-title":"A Review of the Cholinergic System and Therapeutic Approaches to Treat Brain Disorders","volume":"45","author":"Bertrand","year":"2020","journal-title":"Curr. 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