{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T19:18:56Z","timestamp":1770923936836,"version":"3.50.1"},"reference-count":25,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To systematically evaluate the diagnostic efficacy of Al\u00b9\u2078F-NOTA-FAPI-04 PET\/CT in breast cancer and explore the correlation between tracer uptake parameters and pathological features of breast cancer based on single-centre, retrospective data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single-center retrospective study enrolled 58 female patients with suspected primary breast cancer who underwent Al\u00b9\u2078F-NOTA-FAPI-04 PET\/CT before surgery or core needle biopsy (February 2023\u2013November 2025). Lesion maximum\/mean standardized uptake values (SUVmax\/SUVmean) were measured via region-of-interest analysis. Semi-quantitative positivity thresholds (SUVmax\u2009&gt;\u20092.5 or tumor-to-background ratio\u2009\u2265\u20091.5) were used for lesion classification. Diagnostic efficacy (sensitivity, specificity, accuracy) was calculated with pathological results as the gold standard, and 95% confidence intervals (CIs) were determined via the Clopper\u2013Pearson exact method. Differences in uptake parameters across pathological types, molecular subtypes, and immunohistochemical (ER\/PR\/HER2\/Ki-67) statuses were analyzed using Mann\u2013Whitney U or Kruskal\u2013Wallis H tests.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 58 patients, 49 had breast cancer and 9 had benign lesions. Al\u00b9\u2078F-NOTA-FAPI-04 PET\/CT achieved a sensitivity of 95.9% (95% CI: 86.3%\u201399.5%), specificity of 88.9% (95% CI: 51.9%\u201399.7%), and accuracy of 94.8% (95% CI: 85.8%\u201398.9%). All 53 primary lesions were detected (detection rate: 100%), and the detection rate for 87 lymph node metastases was 96.5%. SUVmax\/SUVmean of malignant lesions (median [IQR]: 13.20 [9.55\u201317.85]\/8.15 [5.68\u201310.92]) were significantly higher than those of benign lesions (2.13 [1.56\u20132.89]\/1.35 [0.98\u20131.86], both\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). No statistically significant differences in uptake parameters were observed across pathological types, molecular subtypes, or ER\/PR\/HER2\/Ki-67 statuses (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&gt;\u20090.05), though numerical trends existed; this may be attributed to Type II error due to small subgroup sizes and insufficient statistical power (29.7%\u201362.3% for detecting medium-to-large effect sizes). No correlation was found between lesion size and uptake parameters (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.186 for SUVmax,\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.165 for SUVmean, both\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&gt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Al\u00b9\u2078F-NOTA-FAPI-04 PET\/CT exhibits high sensitivity and accuracy for breast cancer diagnosis and lymph node metastasis detection, with uptake independent of blood glucose levels. Its core clinical roles include complementary initial diagnosis in high-risk subgroups (dense breasts, diabetes), primary nodal staging, and problem-solving in equivocal cases. However, the lack of significant correlation between uptake parameters and pathological features should be interpreted cautiously due to potential Type II error. These characteristics make it a versatile imaging tool for breast cancer diagnosis and staging in regional tertiary care settings, with further validation needed in larger, balanced cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0342769","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T18:29:16Z","timestamp":1770920956000},"page":"e0342769","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Al18F-NOTA-FAPI-04 PET\/CT for diagnosis of breast cancer and its correlation with pathological features: A single-center retrospective study"],"prefix":"10.1371","volume":"21","author":[{"given":"Yi","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijuan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Limeng","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3487-5795","authenticated-orcid":true,"given":"Hao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"issue":"9","key":"pone.0342769.ref001","first-page":"1185","article-title":"Disease burden and economic burden of breast cancer in females in China: a synthesis analysis","volume":"45","author":"XY Zhou","year":"2024","journal-title":"Zhonghua Liu Xing Bing Xue Za Zhi"},{"issue":"3","key":"pone.0342769.ref002","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"H Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"issue":"3","key":"pone.0342769.ref003","doi-asserted-by":"crossref","first-page":"262","DOI":"10.3390\/bioengineering11030262","article-title":"Evaluating the Role of Breast Ultrasound in Early Detection of Breast Cancer in Low- and Middle-Income Countries: A Comprehensive Narrative Review","volume":"11","author":"R Iacob","year":"2024","journal-title":"Bioengineering (Basel)"},{"issue":"2","key":"pone.0342769.ref004","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1007\/s00259-021-05492-z","article-title":"AI-enhanced simultaneous multiparametric 18F-FDG PET\/MRI for accurate breast cancer diagnosis","volume":"49","author":"V Romeo","year":"2022","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"1","key":"pone.0342769.ref005","first-page":"209","article-title":"Diagnostic value of ultrasound combined with magnetic resonance imaging in different stages of breast cancer","volume":"17","author":"Q Pan","year":"2019","journal-title":"Oncol Lett"},{"issue":"9","key":"pone.0342769.ref006","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1007\/s00259-015-3070-1","article-title":"Association between \u00b9\u2078F-FDG uptake and molecular subtype of breast cancer","volume":"42","author":"K Kitajima","year":"2015","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"pone.0342769.ref007","doi-asserted-by":"crossref","first-page":"110661","DOI":"10.1016\/j.ejrad.2022.110661","article-title":"Relationship between FDG-PET and the immune microenvironment in breast cancer","volume":"158","author":"K Kitajima","year":"2023","journal-title":"Eur J Radiol"},{"issue":"6","key":"pone.0342769.ref008","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1007\/s00259-020-05132-y","article-title":"Biodistribution, pharmacokinetics, dosimetry of [68Ga]Ga-DOTA.SA.FAPi, and the head-to-head comparison with [18F]F-FDG PET\/CT in patients with various cancers","volume":"48","author":"S Ballal","year":"2021","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"pone.0342769.ref009","doi-asserted-by":"crossref","first-page":"1047010","DOI":"10.3389\/fonc.2022.1047010","article-title":"Prospective comparison of 68Ga-FAPI-04 and 18F-FDG PET\/CT for tumor staging in nasopharyngeal carcinoma","volume":"12","author":"H Ding","year":"2022","journal-title":"Front Oncol"},{"issue":"13","key":"pone.0342769.ref010","doi-asserted-by":"crossref","first-page":"4259","DOI":"10.1007\/s00259-021-05470-5","article-title":"Clinical translational evaluation of Al18F-NOTA-FAPI for fibroblast activation protein-targeted tumour imaging","volume":"48","author":"S Wang","year":"2021","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"3","key":"pone.0342769.ref011","doi-asserted-by":"crossref","DOI":"10.1097\/RLU.0000000000005617","article-title":"FAP-Targeted SPECT\/CT and PET\/CT Imaging for Breast Cancer Patients","volume":"50","author":"J McGale","year":"2025","journal-title":"Clin Nucl Med"},{"issue":"13","key":"pone.0342769.ref012","doi-asserted-by":"crossref","first-page":"4396","DOI":"10.1007\/s00259-021-05475-0","article-title":"State-of-the-art of FAPI-PET imaging: a systematic review and meta-analysis","volume":"48","author":"M Sollini","year":"2021","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"pone.0342769.ref013","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.breast.2021.07.019","article-title":"Dissecting the biological heterogeneity of HER2-positive breast cancer","volume":"59","author":"F Schettini","year":"2021","journal-title":"Breast"},{"issue":"7","key":"pone.0342769.ref014","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.2967\/jnumed.121.262426","article-title":"Correlation of 68Ga-FAPi-46 PET Biodistribution with FAP Expression by Immunohistochemistry in Patients with Solid Cancers: Interim Analysis of a Prospective Translational Exploratory Study","volume":"63","author":"CE Mona","year":"2022","journal-title":"J Nucl Med"},{"issue":"8","key":"pone.0342769.ref015","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1007\/s12149-023-01852-x","article-title":"What radiolabeled FAPI pet can add in breast cancer? A systematic review from literature","volume":"37","author":"L Evangelista","year":"2023","journal-title":"Ann Nucl Med"},{"issue":"1","key":"pone.0342769.ref016","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.acra.2024.07.058","article-title":"Comparison of 18F-FDG PET\/CT and 18F-FAPI PET\/CT in Systemic Staging of Newly Diagnosed Breast Cancer","volume":"32","author":"J Bin","year":"2025","journal-title":"Acad Radiol"},{"issue":"4","key":"pone.0342769.ref017","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.jcmgh.2022.12.005","article-title":"Fibroblast Activation Protein Activates Macrophages and Promotes Parenchymal Liver Inflammation and Fibrosis","volume":"15","author":"A-T Yang","year":"2023","journal-title":"Cell Mol Gastroenterol Hepatol"},{"issue":"12","key":"pone.0342769.ref018","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.3390\/diagnostics13122018","article-title":"FAPI PET\/CT Imaging-An Updated Review","volume":"13","author":"KR Chandekar","year":"2023","journal-title":"Diagnostics (Basel)"},{"issue":"12","key":"pone.0342769.ref019","doi-asserted-by":"crossref","first-page":"3459","DOI":"10.3390\/jcm13123459","article-title":"PET Molecular Imaging in Breast Cancer: Current Applications and Future Perspectives","volume":"13","author":"S Katal","year":"2024","journal-title":"J Clin Med"},{"issue":"8","key":"pone.0342769.ref020","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1007\/s00259-023-06169-5","article-title":"A radiohybrid theranostics ligand labeled with fluorine-18 and lutetium-177 for fibroblast activation protein-targeted imaging and radionuclide therapy","volume":"50","author":"T Yang","year":"2023","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"11","key":"pone.0342769.ref021","doi-asserted-by":"crossref","first-page":"3651","DOI":"10.1007\/s00259-022-05842-5","article-title":"Preclinical evaluation of FAP-2286 for fibroblast activation protein targeted radionuclide imaging and therapy","volume":"49","author":"D Zboralski","year":"2022","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"1","key":"pone.0342769.ref022","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1007\/s00259-024-06873-w","article-title":"Exploring the value of FAP-targeted PET\/CT in differentiating breast cancer molecular subtypes: a preliminary study","volume":"52","author":"T Liu","year":"2024","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"13","key":"pone.0342769.ref023","doi-asserted-by":"crossref","first-page":"4694","DOI":"10.7150\/thno.88335","article-title":"Evaluation of FAPI PET imaging in gastric cancer: a systematic review and meta-analysis","volume":"13","author":"D Ruan","year":"2023","journal-title":"Theranostics"},{"issue":"49","key":"pone.0342769.ref024","doi-asserted-by":"crossref","first-page":"67523","DOI":"10.1021\/acsami.4c17912","article-title":"Comparative Study of [18F]AlF-LNC1007, [18F]FDG, and [18F]AlF-NOTA-FAPI-04 PET\/CT in Breast Cancer Diagnosis: A Methodological Exploration and Analytical Insight","volume":"16","author":"H Gao","year":"2024","journal-title":"ACS Appl Mater Interfaces"},{"issue":"4","key":"pone.0342769.ref025","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/pro6.1245","article-title":"[18F]-NOTA-FAPI-04 PET\/CT downgraded the staging of a breast cancer patient and changed their treatment management","volume":"8","author":"J Qin","year":"2024","journal-title":"Precis Radiat Oncol"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0342769","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T18:29:20Z","timestamp":1770920960000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0342769"}},"subtitle":[],"editor":[{"given":"Francesco","family":"Dondi","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,2,12]]},"references-count":25,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0342769","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,12]]}}}