{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:24:28Z","timestamp":1790742268123,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T00:00:00Z","timestamp":1748649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health","award":["RF-2021-12372711"],"award-info":[{"award-number":["RF-2021-12372711"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Purpose: The skeletal muscle has been proposed to contribute to the progressive loss of motor neurons typical of amyotrophic lateral sclerosis (ALS). However, this mechanism has not yet been clarified due to the lack of suitable imaging tools. Here, we aimed to verify whether PET imaging of the translocator protein 18 kDa (TSPO) can detect a muscular abnormality in an experimental model of ALS. Methods: In vivo biodistribution and kinetics of [18F]DPA-714 were analyzed in skeletal muscle and brain of SOD1G93A transgenic mice and in wildtype (WT) littermates. Both cohorts were divided into three groups (n = 6 each) to be studied at 60, 90 and 120 days. After microPET imaging, animals were sacrificed to evaluate inflammatory infiltrates by hematoxylin\/eosin staining and TSPO expression by immunohistochemistry and Western blot in both quadriceps and brain. Results: [18F]DPA-714 uptake was higher in the skeletal muscles of SOD1G93A than in WT mice in the preclinical phase (60 and 90 days) and further increased up to the symptomatic late stage (120 days). Inflammatory cells were absent in the quadriceps of SOD1G93A mice whose myocytes, instead, showed a progressive increase in TSPO expression with advancing age. By contrast, brain tracer uptake and TSPO expression were comparably low in both groups, regardless of age and genotype. Conclusion: Upregulation of TSPO expression is characteristic of skeletal muscle, but not the brain, in the experimental SOD1G93A mouse model of ALS. Tracers targeting this pathway have been mostly proposed for the evaluation of inflammatory processes within the central nervous system. Nevertheless, the ubiquitous nature of TSPO expression and its responsiveness to various signals may broaden the diagnostic potential of these tracers to include disease conditions beyond inflammation.<\/jats:p>","DOI":"10.3390\/biom15060799","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T12:27:09Z","timestamp":1748867229000},"page":"799","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Increased [18F]DPA-714 Uptake in the Skeletal Muscle of SOD1G93A Mice: A New Potential of Translocator Protein 18 kDa Imaging in Amyotrophic Lateral Sclerosis"],"prefix":"10.3390","volume":"15","author":[{"given":"Cecilia","family":"Marini","sequence":"first","affiliation":[{"name":"Institute of BioImaging and Complex Biological Systems, National Research Council (CNR), 20054 Milan, Italy"},{"name":"Nuclear Medicine, IRCCS Ospedale Policlinico San Martino di Genova, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9046-7170","authenticated-orcid":false,"given":"Mattia","family":"Riondato","sequence":"additional","affiliation":[{"name":"Nuclear Medicine, IRCCS Ospedale Policlinico San Martino di Genova, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Dighero","sequence":"additional","affiliation":[{"name":"Nuclear Medicine, Department of Health Science, University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Democrito","sequence":"additional","affiliation":[{"name":"Nuclear Medicine, IRCCS Ospedale Policlinico San Martino di Genova, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Losacco","sequence":"additional","affiliation":[{"name":"Nuclear Medicine, IRCCS Ospedale Policlinico San Martino di Genova, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Emionite","sequence":"additional","affiliation":[{"name":"Animal Facility, IRCCS Ospedale Policlinico San Martino di Genova, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2150-3953","authenticated-orcid":false,"given":"Lucilla","family":"Nobbio","sequence":"additional","affiliation":[{"name":"Clinica Neurologica Unit, IRCCS Ospedale Policlinico San Martino di Genova, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Di Patrizi","sequence":"additional","affiliation":[{"name":"Radiology Unit, IRCCS Ospedale Policlinico San Martino di Genova, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4257-0629","authenticated-orcid":false,"given":"Mattia","family":"Camera","sequence":"additional","affiliation":[{"name":"DINOGMI, University of Genova, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Ghersi","sequence":"additional","affiliation":[{"name":"Nuclear Medicine, IRCCS Ospedale Policlinico San Martino di Genova, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8211-1343","authenticated-orcid":false,"given":"Maddalena","family":"Ghelardoni","sequence":"additional","affiliation":[{"name":"Nuclear Medicine, IRCCS Ospedale Policlinico San Martino di Genova, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6043-9627","authenticated-orcid":false,"given":"Francesco","family":"Lanfranchi","sequence":"additional","affiliation":[{"name":"Nuclear Medicine, Department of Health Science, University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Vitale","sequence":"additional","affiliation":[{"name":"Nuclear Medicine, IRCCS Ospedale Policlinico San Martino di Genova, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1278-9761","authenticated-orcid":false,"given":"Sonia","family":"Carta","sequence":"additional","affiliation":[{"name":"Nuclear Medicine, IRCCS Ospedale Policlinico San Martino di Genova, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Chiesa","sequence":"additional","affiliation":[{"name":"Nuclear Medicine, IRCCS Ospedale Policlinico San Martino di Genova, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2236-5142","authenticated-orcid":false,"given":"Carola","family":"Torazza","sequence":"additional","affiliation":[{"name":"Pharmacology, Department of Pharmacy, University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3384-0666","authenticated-orcid":false,"given":"Marco","family":"Milanese","sequence":"additional","affiliation":[{"name":"Pharmacology, Department of Pharmacy, University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1937-9116","authenticated-orcid":false,"given":"Matteo","family":"Bauckneht","sequence":"additional","affiliation":[{"name":"Nuclear Medicine, IRCCS Ospedale Policlinico San Martino di Genova, 16132 Genoa, Italy"},{"name":"Nuclear Medicine, Department of Health Science, University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9371-4832","authenticated-orcid":false,"given":"Mehrnaz","family":"Hamedani","sequence":"additional","affiliation":[{"name":"DINOGMI, University of Genova, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Zaottini","sequence":"additional","affiliation":[{"name":"Radiology, Department of Health Science, University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2604-7830","authenticated-orcid":false,"given":"Angelo","family":"Schenone","sequence":"additional","affiliation":[{"name":"Clinica Neurologica Unit, IRCCS Ospedale Policlinico San Martino di Genova, 16132 Genoa, Italy"},{"name":"DINOGMI, University of Genova, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Martinoli","sequence":"additional","affiliation":[{"name":"Radiology, Department of Health Science, University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6477-3182","authenticated-orcid":false,"given":"Federica","family":"Grillo","sequence":"additional","affiliation":[{"name":"Pathology Unit, IRCCS Ospedale Policlinico San Martino di Genova, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianmario","family":"Sambuceti","sequence":"additional","affiliation":[{"name":"Nuclear Medicine, IRCCS Ospedale Policlinico San Martino di Genova, 16132 Genoa, Italy"},{"name":"Nuclear Medicine, Department of Health Science, University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/s41573-022-00612-2","article-title":"Amyotrophic lateral sclerosis: A neurodegenerative disorder poised for successful therapeutic 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