{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:13:20Z","timestamp":1788459200232,"version":"build-2803163510"},"reference-count":21,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015375","name":"Affiliated Hospital of Southwest Medical University","doi-asserted-by":"publisher","award":["2021ZKQN054"],"award-info":[{"award-number":["2021ZKQN054"]}],"id":[{"id":"10.13039\/501100015375","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015375","name":"Affiliated Hospital of Southwest Medical University","doi-asserted-by":"publisher","award":["2022QN055"],"award-info":[{"award-number":["2022QN055"]}],"id":[{"id":"10.13039\/501100015375","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Thyroglobulin (Tg) is a standard biomarker for monitoring differentiated thyroid carcinoma (DTC) after radioiodine therapy, yet its reliability is compromised by false-positive and false-negative results. This study aimed to evaluate the diagnostic performance of\n                      <jats:sup>68<\/jats:sup>\n                      Ga-FAPI-04 PET\/CT, an emerging imaging modality, for detecting recurrence and metastasis in DTC patients, regardless of their Tg status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective study included patients with suspected or confirmed metastatic DTC who underwent\n                      <jats:sup>68<\/jats:sup>\n                      Ga-FAPI-04 PET\/CT between October 2022 and May 2025. All participants underwent\n                      <jats:sup>68<\/jats:sup>\n                      Ga-FAPI-04 PET\/CT and Tg testing, with histopathology or clinical follow-up as the reference standard. The sensitivity, specificity, and accuracy of both methods were compared. Quantitative analysis was performed using the target-to-background ratio (TBR).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 99 patients in a TSH-suppressed state,\n                      <jats:sup>68<\/jats:sup>\n                      Ga-FAPI-04 PET\/CT demonstrated superior diagnostic accuracy (95.96%) compared to Tg testing (91.92%). In 48 TSH-stimulated patients, PET\/CT maintained perfect accuracy (100%), outperforming Tg (97.92%). Notably, PET\/CT successfully identified metastatic lesions in eight Tg-negative patients, primarily lymph node metastases. Using the mediastinum as a background for TBR calculation further enhanced the diagnostic efficacy for lymph node metastases, with the optimal threshold being 1.428, and achieving an accuracy and true positive rate of 0.98.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:sup>68<\/jats:sup>\n                      Ga\u2011FAPI\u201104 PET\/CT exhibits high accuracy for diagnosing recurrence and metastasis in DTC, and importantly can identify lesions in Tg\u2011negative patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0355343","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:21:01Z","timestamp":1788456061000},"page":"e0355343","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["68Ga-FAPI-04 PET\/CT has high diagnostic efficacy in Tg-positive and Tg-negative differentiated thyroid cancer"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4183-4063","authenticated-orcid":true,"given":"Lixian","family":"Mou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0052-7817","authenticated-orcid":true,"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"issue":"4","key":"pone.0355343.ref001","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/S2213-8587(22)00035-3","article-title":"The epidemiological landscape of thyroid cancer worldwide: GLOBOCAN estimates for incidence and mortality rates in 2020","volume":"10","author":"M Pizzato","year":"2022","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"1","key":"pone.0355343.ref002","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/thy.2015.0020","article-title":"2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer","volume":"26","author":"BR Haugen","year":"2016","journal-title":"Thyroid"},{"key":"pone.0355343.ref003","first-page":"3676886","article-title":"Effectiveness and Safety of Levothyroxine Tablets Combined with Iodine-131 in the Treatment of Thyroid Cancer","volume":"2022","author":"Y Bai","year":"2022","journal-title":"J Oncol"},{"issue":"11","key":"pone.0355343.ref004","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1089\/thy.2012.0190","article-title":"Postoperative stimulated thyroglobulin of less than 1 ng\/ml as a criterion to spare low-risk patients with papillary thyroid cancer from radioactive iodine ablation","volume":"22","author":"PW Rosario","year":"2012","journal-title":"Thyroid"},{"key":"pone.0355343.ref005","doi-asserted-by":"crossref","first-page":"796471","DOI":"10.1155\/2015\/796471","article-title":"Is Stimulated Thyroglobulin Necessary after Ablation in All Patients with Papillary Thyroid Carcinoma and Basal Thyroglobulin Detectable by a Second-Generation Assay?","volume":"2015","author":"PW Rosario","year":"2015","journal-title":"Int J Endocrinol"},{"key":"pone.0355343.ref006","doi-asserted-by":"crossref","first-page":"398194","DOI":"10.1155\/2013\/398194","article-title":"Thyroid Lobectomy Is Associated with Excellent Clinical Outcomes in Properly Selected Differentiated Thyroid Cancer Patients with Primary Tumors Greater Than 1\u2009cm","volume":"2013","author":"F Vaisman","year":"2013","journal-title":"J Thyroid Res"},{"issue":"9","key":"pone.0355343.ref007","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1089\/thy.2021.0125","article-title":"Patient-Tailored Levothyroxine Dosage with Pharmacokinetic\/Pharmacodynamic Modeling: A Novel Approach After Total Thyroidectomy","volume":"31","author":"VH Brun","year":"2021","journal-title":"Thyroid"},{"issue":"5","key":"pone.0355343.ref008","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/s41575-019-0115-0","article-title":"Cancer-associated fibroblasts in gastrointestinal cancer","volume":"16","author":"H Kobayashi","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"1","key":"pone.0355343.ref009","doi-asserted-by":"crossref","DOI":"10.1148\/rycan.2019194003","article-title":"68Ga FAPI PET\/CT: Tracer Uptake in 28 Different Kinds of Cancer","volume":"1","author":"DK Hathi","year":"2019","journal-title":"Radiol Imaging Cancer"},{"key":"pone.0355343.ref010","doi-asserted-by":"crossref","first-page":"925100","DOI":"10.3389\/fonc.2022.925100","article-title":"Comparison of Diagnostic Efficacy of [(68)Ga]Ga-FAPI-04 and [(18)F]FDG PET\/CT for Staging and Restaging of Gastric Cancer","volume":"12","author":"S Zhang","year":"2022","journal-title":"Front Oncol"},{"key":"pone.0355343.ref011","doi-asserted-by":"crossref","first-page":"1202505","DOI":"10.3389\/fonc.2023.1202505","article-title":"Head-to-head comparison of (68)Ga-FAPI-04 PET\/CT and (18)F-FDG PET\/CT in the evaluation of primary digestive system cancer: a systematic review and meta-analysis","volume":"13","author":"J Ouyang","year":"2023","journal-title":"Front Oncol"},{"issue":"4","key":"pone.0355343.ref012","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1007\/s00259-023-06539-z","article-title":"Comparison of the diagnostic value of [(68) Ga]Ga-FAPI-04 PET\/MR and [(18)F]FDG PET\/CT in patients with T stage\u2009\u2264\u20092a2 uterine cervical cancer: a prospective study","volume":"51","author":"Y Lyu","year":"2024","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"5","key":"pone.0355343.ref013","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1097\/RLU.0000000000003569","article-title":"68Ga-FAPI PET\/CT in Thyroid Cancer With Thyroglobulin Elevation and Negative Iodine Scintigraphy","volume":"46","author":"H Fu","year":"2021","journal-title":"Clin Nucl Med"},{"issue":"3","key":"pone.0355343.ref014","doi-asserted-by":"crossref","first-page":"386","DOI":"10.2967\/jnumed.118.215913","article-title":"68Ga-FAPI PET\/CT: Biodistribution and Preliminary Dosimetry Estimate of 2 DOTA-Containing FAP-Targeting Agents in Patients with Various Cancers","volume":"60","author":"FL Giesel","year":"2019","journal-title":"J Nucl Med"},{"issue":"7","key":"pone.0355343.ref015","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1007\/s12149-022-01742-8","article-title":"68)Ga-DOTA-FAPI-04 PET\/CT imaging in radioiodine-refractory differentiated thyroid cancer (RR-DTC) patients","volume":"36","author":"Y Chen","year":"2022","journal-title":"Ann Nucl Med"},{"issue":"1","key":"pone.0355343.ref016","first-page":"21","article-title":"Advances in thyroglobulin assays and their impact on the management of differentiated thyroid cancers","volume":"74","author":"M d\u2019Herbomez","year":"2016","journal-title":"Ann Biol Clin (Paris)"},{"issue":"6","key":"pone.0355343.ref017","article-title":"SNMMI Procedure Standard\/EANM Practice Guideline for Nuclear Medicine Evaluation and Therapy of Differentiated Thyroid Cancer: Abbreviated Version","volume":"63","author":"AM Avram","year":"2022","journal-title":"J Nucl Med"},{"issue":"5","key":"pone.0355343.ref018","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1111\/j.1365-2265.2011.04278.x","article-title":"Incidence and implications of negative serum thyroglobulin but positive I-131 whole-body scans in patients with well-differentiated thyroid cancer prepared with rhTSH or thyroid hormone withdrawal","volume":"76","author":"MH Cherk","year":"2012","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"8","key":"pone.0355343.ref019","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1515\/CCLM.2009.230","article-title":"Heterophile antibodies may falsely increase or decrease thyroglobulin measurement in patients with differentiated thyroid carcinoma","volume":"47","author":"L Giovanella","year":"2009","journal-title":"Clin Chem Lab Med"},{"issue":"2","key":"pone.0355343.ref020","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1148\/radiol.212430","article-title":"68Ga Fibroblast Activation Protein Inhibitor PET\/CT in the Detection of Metastatic Thyroid Cancer: Comparison with 18F-FDG PET\/CT","volume":"304","author":"H Fu","year":"2022","journal-title":"Radiology"},{"issue":"12","key":"pone.0355343.ref021","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.2967\/jnumed.123.266079","article-title":"68)Ga-Labeled Fibroblast Activation Protein Inhibitor PET\/CT for the Early and Late Prediction of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer Patients: A Prospective Study","volume":"64","author":"L Chen","year":"2023","journal-title":"J Nucl Med"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0355343","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:21:06Z","timestamp":1788456066000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0355343"}},"subtitle":[],"editor":[{"given":"Francesco","family":"Dondi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":21,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0355343","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]}}}