{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:06:20Z","timestamp":1790154380720,"version":"4.0.1"},"reference-count":39,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Differentiating tumor recurrence from treatment-related changes in patients with glioma remains a major diagnostic challenge because conventional MRI has limited specificity. Amino acid positron emission tomography (PET) has emerged as a promising adjunctive imaging modality. Purpose: To evaluate the diagnostic performance of amino acid PET for distinguishing tumor recurrence from treatment-related changes in previously treated glioma patients. Methods: A systematic review and meta-analysis were conducted according to the PRISMA-DTA guidelines. PubMed, Scopus, and Web of Science were searched from inception to March 2026. Studies evaluating clinically used amino acid PET tracers (MET, FET, or FDOPA) in previously treated glioma patients and reporting sufficient data to construct 2 \u00d7 2 contingency tables were included. Pooled sensitivity and specificity were estimated using a bivariate random-effects model. The primary analysis was restricted to studies reporting patient-based data from non-overlapping cohorts. A post hoc sensitivity analysis, added in response to peer review, retained both potentially overlapping patient-based datasets. Lesion- and scan-based studies were excluded from quantitative synthesis because within-patient clustering could not be accounted for using the published aggregate data. Subgroup and meta-regression analyses explored sources of heterogeneity. Results: Sixteen studies met the inclusion criteria. The primary synthesis comprised 12 studies reporting patient-based data from non-overlapping cohorts (728 patients, one 2 \u00d7 2 table each). Amino acid PET demonstrated a pooled sensitivity of 0.87 (95% CI 0.83\u20130.90) and specificity of 0.78 (95% CI 0.72\u20130.83). The positive likelihood ratio was 3.91 (95% CI 3.04\u20135.02), the negative likelihood ratio was 0.17 (95% CI 0.13\u20130.23), and the diagnostic odds ratio was 22.8 (95% CI 14.6\u201335.7). At the pooled prevalence of recurrence of 68%, a positive scan corresponded to a post-test probability of 89% and a negative scan to 27%. Univariable I2 estimates were 10% for sensitivity and 0% for specificity, but these measures should not be interpreted as evidence of overall homogeneity. Estimates were essentially unchanged when both potentially overlapping datasets were retained (13 studies, 756 patients). Tracer type was nominally associated with the diagnostic odds ratio (p = 0.044), but tracer type was strongly confounded by study sample size and publication era, and the association was not robust in the sensitivity analysis. No statistically significant subgroup differences were identified; however, these analyses were limited by the small number of studies and methodological heterogeneity. Conclusions: Amino acid PET usefully but not decisively revises the probability of recurrence in patients under suspicion after treatment. At the pooled pre-test probability of 68%, a positive PET increased the post-test probability of recurrence to 89%, whereas a negative PET reduced it to 27%; therefore, a negative result does not exclude recurrence. Because positivity thresholds were largely derived post hoc and reference standards were composite, these estimates are likely to be optimistic. Apparent tracer-related differences observed in subgroup and meta-regression analyses were strongly confounded by publication era and study sample size and were not supported by head-to-head within-patient comparisons. Therefore, no superiority of MET, FET, or FDOPA can be inferred from the available evidence. The analysis was limited to MET, FET, and FDOPA, and the findings may therefore not be generalizable to other amino acid tracers.<\/jats:p>","DOI":"10.3390\/cancers18193069","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:17:54Z","timestamp":1790065074000},"page":"3069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic Accuracy of Amino Acid PET for Differentiating Tumor Recurrence or Progression from Treatment-Related Changes in Glioma Patients: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"18","author":[{"given":"Ma\u0142gorzata","family":"Podstawka","sequence":"first","affiliation":[{"name":"Department of Neurosurgery and Neurooncology, Barlicki University Hospital, Medical University of Lodz, 90-153 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"D\u0119bska","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Neurooncology, Barlicki University Hospital, Medical University of Lodz, 90-153 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2883-5680","authenticated-orcid":false,"given":"Natalia","family":"Koc","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Neurooncology, Barlicki University Hospital, Medical University of Lodz, 90-153 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Chybowski","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Neurooncology, Barlicki University Hospital, Medical University of Lodz, 90-153 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartosz","family":"Szmyd","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Neurooncology, Barlicki University Hospital, Medical University of Lodz, 90-153 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karol","family":"Zaczkowski","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Neurooncology, Barlicki University Hospital, Medical University of Lodz, 90-153 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest J.","family":"Bobeff","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Neurooncology, Barlicki University Hospital, Medical University of Lodz, 90-153 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Ratajczyk","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Therapy, Medical University of Lodz, 90-153 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5648-345X","authenticated-orcid":false,"given":"Bart\u0142omiej","family":"Tomasik","sequence":"additional","affiliation":[{"name":"Department of Oncology and Radiotherapy, Faculty of Medicine, Medical University of Gdansk, 80-210 Gdansk, Poland"},{"name":"Centre for Experimental Cardiooncology, Medical University of Gdansk, 80-210 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariusz J.","family":"Jask\u00f3lski","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Neurooncology, Barlicki University Hospital, Medical University of Lodz, 90-153 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karol","family":"Wi\u015bniewski","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and Neurooncology, Barlicki University Hospital, Medical University of Lodz, 90-153 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"342","DOI":"10.2176\/nmc.38.342","article-title":"Clinical usefulness of 11C-MET PET and 201T1 SPECT for differentiation of recurrent glioma from radiation necrosis","volume":"38","author":"Sonoda","year":"1998","journal-title":"Neurol. Med.-Chir."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/BF02984466","article-title":"Methionine positron emission tomography for differentiation of recurrent brain tumor and radiation necrosis after stereotactic radiosurgery in malignant glioma","volume":"18","author":"Tsuyuguchi","year":"2004","journal-title":"Ann. Nucl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.clineuro.2010.06.005","article-title":"Differentiating radiation necrosis from tumor recurrence in high-grade gliomas: Assessing the efficacy of 18F-FDG PET, 11C-methionine PET and perfusion MRI","volume":"112","author":"Kim","year":"2010","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4129","DOI":"10.1007\/s00330-017-4789-9","article-title":"Diagnostic accuracy of magnetic resonance imaging techniques for treatment response evaluation in patients with high-grade glioma, a systematic review and meta-analysis","volume":"27","author":"Holtman","year":"2017","journal-title":"Eur. Radiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jns.2015.02.038","article-title":"Diagnostic accuracy of diffusion MRI with quantitative ADC measurements in differentiating glioma recurrence from radiation necrosis","volume":"351","author":"Zhang","year":"2015","journal-title":"J. Neurol. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1016\/j.ejrad.2014.09.018","article-title":"Role of magnetic resonance spectroscopy for the differentiation of recurrent glioma from radiation necrosis: A systematic review and meta-analysis","volume":"83","author":"Zhang","year":"2014","journal-title":"Eur. J. Radiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"244","DOI":"10.3390\/cancers4010244","article-title":"Diagnostic value of 11C-methionine and 18F-fluorothymidine PET in recurrent high-grade gliomas: Differentiation from treatment-induced tissue necrosis","volume":"4","author":"Shishido","year":"2012","journal-title":"Cancers"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.2967\/jnumed.114.140608","article-title":"Comparison of the amino acid tracers 18F-FET and 18F-DOPA in high-grade glioma patients","volume":"55","author":"Lapa","year":"2014","journal-title":"J. Nucl. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.ijrobp.2010.07.002","article-title":"An interindividual comparison of O-(2-[18F]fluoroethyl)-L-tyrosine (FET)- and L-[methyl-11C]methionine (MET)-PET in patients with brain gliomas and metastases","volume":"81","author":"Grosu","year":"2011","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Juh\u00e1sz, C., Dwivedi, S., Kamson, D.O., Michelhaugh, S.K., and Mittal, S. (2014). Comparison of amino acid positron emission tomographic radiotracers for molecular imaging of primary and metastatic brain tumors. Mol. Imaging, 13.","DOI":"10.2310\/7290.2014.00015"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yu, P., Wang, Y., Su, F., and Chen, Y. (2024). Comparing [18F]FET PET and [18F]FDOPA PET for glioma recurrence diagnosis: A systematic review and meta-analysis. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1346951"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"91030","DOI":"10.18632\/oncotarget.19024","article-title":"The performance of 11C-methionine PET in the differential diagnosis of glioma recurrence","volume":"8","author":"Xu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_13","first-page":"85","article-title":"The value of 11C-methionine PET in the early differentiation between tumour recurrence and radionecrosis in patients treated for a high-grade glioma and indeterminate MRI","volume":"36","author":"Garcia","year":"2017","journal-title":"Rev. Esp. Med. Nucl. Imagen Mol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1097\/RLU.0000000000000532","article-title":"11C-MET PET\/CT and advanced MRI in the evaluation of tumor recurrence in high-grade gliomas","volume":"39","author":"Sharma","year":"2014","journal-title":"Clin. Nucl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"280","DOI":"10.2176\/nmc.oa2013-0117","article-title":"Comparison of 11C-methionine, 11C-choline, and 18F-FDG PET for distinguishing glioma recurrence from radiation necrosis","volume":"54","author":"Takenaka","year":"2014","journal-title":"Neurol. Med.-Chir."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1007\/s00259-017-3916-9","article-title":"11C-MET PET\/MRI for detection of recurrent glioma","volume":"45","author":"Deuschl","year":"2018","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1007\/s00259-013-2384-0","article-title":"18F-FDOPA PET\/CT for detection of recurrence in patients with glioma: Prospective comparison with 18F-FDG PET\/CT","volume":"40","author":"Karunanithi","year":"2013","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1007\/s00330-013-2838-6","article-title":"Comparative diagnostic accuracy of contrast-enhanced MRI and 18F-FDOPA PET-CT in recurrent glioma","volume":"23","author":"Karunanithi","year":"2013","journal-title":"Eur. Radiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1093\/neuonc\/not166","article-title":"Comparison of visual and semiquantitative analysis of 18F-FDOPA PET\/CT for recurrence detection in glioblastoma patients","volume":"16","author":"Herrmann","year":"2014","journal-title":"Neuro-Oncology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s00259-015-3018-5","article-title":"Volumetric assessment of recurrent or progressive gliomas: Comparison between FDOPA PET and perfusion-weighted MRI","volume":"42","author":"Cicone","year":"2015","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13550-020-00645-x","article-title":"Use of static and dynamic FDOPA PET parameters for detecting glioma recurrence or progression","volume":"10","author":"Zaragori","year":"2020","journal-title":"EJNMMI Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"293","DOI":"10.4103\/neuroindia.NI_101_16","article-title":"Potential for differentiation of glioma recurrence from radionecrosis using integrated 18F-FET PET\/MRI: A prospective evaluation","volume":"65","author":"Sogani","year":"2017","journal-title":"Neurol. India"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1111\/jon.12914","article-title":"Brain FET PET tumor-to-white matter ratio to differentiate recurrence from post-treatment changes in high-grade gliomas","volume":"31","author":"Puranik","year":"2021","journal-title":"J. Neuroimaging"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"vdab044","DOI":"10.1093\/noajnl\/vdab044","article-title":"Combined 18F-FET PET and diffusion kurtosis MRI in posttreatment glioblastoma","volume":"3","author":"Grinberg","year":"2021","journal-title":"Neuro-Oncol. Adv."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Celli, M., Caroli, P., Amadori, E., Arpa, D., Gurrieri, L., Ghigi, G., Cenni, P., Paganelli, G., and Matteucci, F. (2021). Diagnostic and prognostic potential of 18F-FET PET in the differential diagnosis of glioma recurrence. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.721821"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1097\/RLU.0000000000003728","article-title":"Does Qualitative Simultaneous 18F-DOPA PET\/mp-MRI Improve Diagnostic Workup? An Initial Experience","volume":"46","author":"Jena","year":"2021","journal-title":"Clin. Nucl. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ahrari, S., Zaragori, T., Rozenblum, L., Oster, J., Imbert, L., Kas, A., and Verger, A. (2021). Dynamic FDOPA PET radiomics for differentiation of glioma progression. Biomedicines, 9.","DOI":"10.3390\/biomedicines9121924"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1007\/s00259-020-05114-0","article-title":"Sequential DSC-MR perfusion and dynamic FET PET for differentiation of glioma progression","volume":"48","author":"Steidl","year":"2021","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4677","DOI":"10.1007\/s00259-022-05917-3","article-title":"Diagnostic yield of simultaneous dynamic contrast-enhanced magnetic resonance perfusion measurements and [18F]FET PET in patients with suspected recurrent anaplastic astrocytoma and glioblastoma","volume":"49","author":"Henriksen","year":"2022","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s11060-022-04089-2","article-title":"Static FET PET radiomics for differentiation of treatment-related changes from glioma progression","volume":"159","author":"Winz","year":"2022","journal-title":"J. Neuro-Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.1007\/s11547-024-01862-3","article-title":"Perfusion MRI and FDOPA PET\/CT in differentiating glioma recurrence","volume":"129","author":"Moltoni","year":"2024","journal-title":"Radiol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s00062-023-01372-1","article-title":"Multiparametric analysis combining DSC-MR perfusion and FET PET","volume":"34","author":"Panholzer","year":"2024","journal-title":"Clin. Neuroradiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1007\/s00330-022-09221-4","article-title":"Differentiating glioma progression from treatment-related changes with dynamic FDOPA PET","volume":"33","author":"Rozenblum","year":"2023","journal-title":"Eur. Radiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s11060-023-04529-7","article-title":"Individualized discrimination of tumor progression using methionine PET","volume":"165","author":"Chen","year":"2023","journal-title":"J. Neuro-Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sahu, A., Mathew, R., Ashtekar, R., Dasgupta, A., Puranik, A., Mahajan, A., Janu, A., Choudhari, A., Desai, S., and Patnam, N.G. (2023). Complementary role of MRI and FET PET in high-grade gliomas. Front. Nucl. Med., 3.","DOI":"10.3389\/fnume.2023.1040998"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s00234-024-03495-9","article-title":"FET PET to differentiate post-treatment changes from recurrence in high-grade gliomas","volume":"67","author":"Puranik","year":"2025","journal-title":"Neuroradiology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s41824-021-00109-y","article-title":"Combined amino acid PET-MRI for identifying recurrence in post-treatment gliomas: Together we grow","volume":"5","author":"Jabeen","year":"2021","journal-title":"Eur. J. Hybrid. Imaging"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4572","DOI":"10.1038\/s41467-023-39731-8","article-title":"Combining amino acid PET and MRI imaging increases accuracy to define malignant areas in adult glioma","volume":"14","author":"Harat","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/19\/3069\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T08:28:58Z","timestamp":1790152138000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/19\/3069"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":39,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["cancers18193069"],"URL":"https:\/\/doi.org\/10.3390\/cancers18193069","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]}}}