{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:58:42Z","timestamp":1790402322430,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    X\u2010linked adrenoleukodystrophy (X\u2010ALD) is a peroxisomal disorder caused by pathogenic variants in\n                    <jats:italic>ABCD1<\/jats:italic>\n                    , resulting in the accumulation of very long\u2010chain fatty acids and risk of progressive neuroinflammatory demyelination in the cerebral form of ALD. Brain MRI is the current standard neuroimaging modality for diagnosis and monitoring of central nervous system involvement. However, MRI primarily detects structural abnormalities and may not fully reflect functional impairment, neuroinflammatory activity, or early cerebral involvement. Positron emission tomography (PET) may provide complementary information beyond conventional MRI. Therefore, we aimed to review the current literature on PET imaging in X\u2010ALD. A systematic literature search was conducted in accordance with PRISMA guidelines using MEDLINE and Embase databases up to April 26, 2026. Studies evaluating brain PET imaging in individuals with X\u2010ALD were included. Data on study design, phenotype,\n                    <jats:italic>ABCD1<\/jats:italic>\n                    genotype, brain MRI findings, PET tracers, analytic methods, and key findings were extracted. A total of 48 records were screened, resulting in the inclusion of 10 case reports and one case series comprising 12 patients. PET tracers included\n                    <jats:sup>18<\/jats:sup>\n                    F\u2010fluorodeoxyglucose (FDG) (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200919 patients),\n                    <jats:sup>11<\/jats:sup>\n                    C\u2010(R)\u2010PK11195 (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20091), and L\u2010[methyl\u2010\n                    <jats:sup>11<\/jats:sup>\n                    C]methionine (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20091). One additional patient underwent PET assessment of cerebral blood flow and oxygen metabolism using unspecified tracers. In FDG\u2010PET studies, cortical hypermetabolism was reported in 12\/19 individuals, whereas cortical hypometabolism was observed in 18\/19 individuals, with findings in one case being either not specified or inconclusive. FDG\u2010PET demonstrated cortical glucose hypometabolism overlying the affected white matter (WM) in 6\/18 individuals with T2 and\/or FLAIR\u2010hyperintense WM lesions on MRI. FDG\u2010PET demonstrated cortical glucose hypometabolism in 12\/18 individuals without WM lesions on MRI. The FDG\u2010PET findings were reported to correlate with clinical symptoms. Neuroinflammation\u2010targeted\n                    <jats:sup>11<\/jats:sup>\n                    C\u2010(R)\u2010PK11195 PET demonstrated increased tracer binding in active WM lesions. Similarly, protein synthesis\u2010targeted L\u2010[methyl\u2010\n                    <jats:sup>11<\/jats:sup>\n                    C]methionine PET demonstrated increased tracer uptake in active WM lesions. PET may detect functional and neuroinflammatory abnormalities beyond those identified by structural MRI in individuals with X\u2010ALD, suggesting a potential role in evaluating the extent and severity of brain involvement. However, the available evidence is limited by small sample sizes, underrepresentation of pediatric and presymptomatic cases, heterogeneous PET tracers and analytic methodologies, and a lack of longitudinal data. Further multimodal and longitudinal studies are needed to establish the clinical utility of PET as a surveillance tool in X\u2010ALD.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70313","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:59:58Z","timestamp":1790398798000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Systematic Review of Positron Emission Tomography (\n                    <scp>PET<\/scp>\n                    ) in X\u2010Linked Adrenoleukodystrophy: Beyond Structural\n                    <scp>MRI<\/scp>"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7278-8242","authenticated-orcid":false,"given":"Yutaka","family":"Furuta","sequence":"first","affiliation":[{"name":"Department of Human Genetics Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9367-0761","authenticated-orcid":false,"given":"Hong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie R.","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Neurology Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9339-531X","authenticated-orcid":false,"suffix":"III","given":"John A.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics and Genomic Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7093-8844","authenticated-orcid":false,"given":"Rory J.","family":"Tinker","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Genomics Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8391-4067","authenticated-orcid":false,"given":"Eishi","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital of Michigan, Detroit Medical Center Wayne State University  Detroit Michigan USA"},{"name":"Department of Neurology, Children's Hospital of Michigan, Detroit Medical Center Wayne State University  Detroit Michigan USA"},{"name":"Translational Imaging Laboratory University Health Center, Detroit Medical Center  Detroit Michigan USA"},{"name":"Translational Neuroscience Program Wayne State University  Detroit Michigan USA"},{"name":"Department of Pediatrics Central Michigan University  Mt. Pleasant Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csaba","family":"Juh\u00e1sz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital of Michigan, Detroit Medical Center Wayne State University  Detroit Michigan USA"},{"name":"Department of Neurology, Children's Hospital of Michigan, Detroit Medical Center Wayne State University  Detroit Michigan USA"},{"name":"Translational Imaging Laboratory University Health Center, Detroit Medical Center  Detroit Michigan USA"},{"name":"Translational Neuroscience Program Wayne State University  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003072\u2010199905000\u201000021"},{"issue":"6","key":"e_1_2_11_3_1","first-page":"1099","article-title":"Concepts of Myelin and Myelination in Neuroradiology","volume":"21","author":"Barkovich A. 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