{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T06:06:52Z","timestamp":1784786812984,"version":"3.55.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      T cell immunoglobulin mucin-3 (TIM-3) plays a critical role in the T cell exhaustion and there have been already many related inhibitory antibodies in clinical trial. However,\n                      <jats:italic>in vivo<\/jats:italic>\n                      non-invasive visualization of TIM-3 is lagging in comparison to the development of therapeutic antibodies. This study aims to develop a positron emission tomography\/computed tomography (PET\/CT) imaging tracer targeting TIM-3 and explore its ability to visualize tumor lesions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A cysteine-modified, NOTA-conjugated peptide, NOTA-P24, was synthesized and radiolabeled with fluorine-18. Its stability and specificity were evaluated\n                      <jats:italic>in vivo<\/jats:italic>\n                      using uptake, competition, and efflux studies. Furthermore, PET\/CT imaging and biodistribution studies were performed on tumor bearing animals.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:sup>18<\/jats:sup>\n                      F]AlF-NOTA-P24 showed high specificity and affinity to TIM-3-expressing cells\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Biodistribution studies on tumor-bearing mice demonstrated high tumoral uptake of the tracer and fast body clearance, resulting in high-contrast images and negligible exposure of healthy tissue to radiation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The work developed a peptide-based probe [\n                      <jats:sup>18<\/jats:sup>\n                      F]AlF-NOTA-P24 targeting TIM-3, with favorable specificity and affinity. This approach has the potential for noninvasive evaluation of TIM-3.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1744607","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:40:44Z","timestamp":1784785244000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and evaluation of a peptide-based radiotracer for targeting TIM-3 in preclinical models"],"prefix":"10.3389","volume":"17","author":[{"given":"Guangfa","family":"Bao","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, The First People\u2019s Hospital of Yunnan Province","place":["Kunming, Yunnan, China"]},{"name":"Yunnan Province Clinical Medical Center for Digestive System Diseases","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, The First People\u2019s Hospital of Yunnan Province","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeqian","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, The First People\u2019s Hospital of Yunnan Province","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, The First People\u2019s Hospital of Yunnan Province","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menglin","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, The First People\u2019s Hospital of Yunnan Province","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rencai","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, The First People\u2019s Hospital of Yunnan Province","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Xv","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, The First People\u2019s Hospital of Yunnan Province","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingkang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, The First People\u2019s Hospital of Yunnan Province","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaobo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, The First People\u2019s Hospital of Yunnan Province","place":["Kunming, Yunnan, China"]},{"name":"Yunnan Province Clinical Medical Center for Digestive System Diseases","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(21)00312-3","article-title":"Lung cancer","volume":"398","author":"Thai","year":"2021","journal-title":"Lancet (London England)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/s0140-6736(16)30958-8","article-title":"Lung cancer: current therapies and new targeted treatments","volume":"389","author":"Hirsch","year":"2017","journal-title":"Lancet (London England)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.35849","article-title":"Immunotherapy for resectable lung cancer","volume":"131","author":"Dennehy","year":"2025","journal-title":"Cancer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2014.59.4358","article-title":"Immune checkpoint blockade in cancer therapy","volume":"33","author":"Postow","year":"2015","journal-title":"J Clin Oncol Off J Am Soc Clin Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2020.38.15_suppl.9621","article-title":"Acquired resistance to PD-1 blockade in NSCLC","volume":"38","author":"Schoenfeld","year":"","journal-title":"J Clin Oncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1038\/nrd.2018.144","article-title":"Overcoming resistance to checkpoint blockade","volume":"17","author":"Crunkhorn","year":"2018","journal-title":"Nat Rev Drug Discov"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-018-0142-8","article-title":"Cancer immunoediting and resistance to T cell-based immunotherapy","volume":"16","author":"O'Donnell","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/s41577-019-0218-4","article-title":"Tumour-intrinsic resistance to immune checkpoint blockade","volume":"20","author":"Kalbasi","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.4c00970","article-title":"Nuclear molecular imaging for evaluating T cell exhaustion","volume":"22","author":"Zhou","year":"2025","journal-title":"Mol Pharmaceutics"},{"key":"B10","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s13045-018-0667-4","article-title":"Tim-3 expression and its role in hepatocellular carcinoma","volume":"11","author":"Liu","year":"2018","journal-title":"J Hematol Oncol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1146\/annurev-immunol-090222-110914","article-title":"T cell exhaustion","volume":"42","author":"Baessler","year":"2024","journal-title":"Annu Rev Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-022-00689-z","article-title":"Clinical implications of T cell exhaustion for cancer immunotherapy","volume":"19","author":"Chow","year":"2022","journal-title":"Nat Rev Clin Oncol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1186\/s12943-019-1091-2","article-title":"Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4","volume":"18","author":"Qin","year":"2019","journal-title":"Mol Cancer"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adf2223","article-title":"Beyond T cell exhaustion: TIM-3 regulation of myeloid cells","volume":"9","author":"Dixon","year":"2024","journal-title":"Sci Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-20-4405","article-title":"Blocking TIM-3 in treatment-refractory advanced solid tumors: a phase Ia\/b study of LY3321367 with or without an anti-PD-L1 antibody","volume":"27","author":"Harding","year":"2021","journal-title":"Clin Cancer Res"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-20-4746","article-title":"Phase I\/Ib clinical trial of sabatolimab, an anti-TIM-3 antibody, alone and in combination with spartalizumab, an anti-PD-1 antibody, in advanced solid tumors","volume":"27","author":"Curigliano","year":"2021","journal-title":"Clin Cancer Res Off J Am Assoc For Cancer Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.Can-13-2908","article-title":"PD-1 and Tim-3 regulate the expansion of tumor antigen-specific CD8+ T cells induced by melanoma vaccines","volume":"74","author":"Fourcade","year":"2014","journal-title":"Cancer Res"},{"key":"B18","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s43556-025-00267-6","article-title":"TIM-3 teams up with PD-1 in cancer immunotherapy: mechanisms and perspectives","volume":"6","author":"Yan","year":"2025","journal-title":"Mol BioMed"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-20-4746","article-title":"Phase I\/Ib clinical trial of sabatolimab, an anti\u2013TIM-3 antibody, alone and in combination with spartalizumab, an anti\u2013PD-1 antibody, in advanced solid tumors","volume":"27","author":"Curigliano","year":"2021","journal-title":"Clin Cancer Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-000911","article-title":"Tim-3 finds its place in the cancer immunotherapy landscape","volume":"8","author":"Acharya","year":"2020","journal-title":"J Immunother Cancer"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.3c01046","article-title":"Construction and preclinical evaluation of (124)I\/(125)I-labeled antibody targeting T cell immunoglobulin and mucin domain-3","volume":"21","author":"Tao","year":"2024","journal-title":"Mol Pharmaceutics"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.4c00884","article-title":"Novel peptide-based (68)Ga-labeled radiotracer for preclinical studies of TIM3 expression","volume":"22","author":"Tao","year":"2025","journal-title":"Mol Pharmaceutics"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/adtp.202000018","article-title":"ImmunoPET imaging of TIM-3 in murine melanoma models","volume":"3","author":"Wei","year":"2020","journal-title":"Adv Ther"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-020-04167-0","article-title":"The biologically functional identification of a novel TIM3-binding peptide P26 in vitro and in vivo","volume":"86","author":"Zhong","year":"2020","journal-title":"Cancer Chemother Pharmacol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.649148","article-title":"FAPI-04 PET\/CT using [(18)F]AlF labeling strategy: automatic synthesis, quality control, and in vivo assessment in patient","volume":"11","author":"Jiang","year":"2021","journal-title":"Front Oncol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.118.210443","article-title":"Development of quinoline-based theranostic ligands for the targeting of fibroblast activation protein","volume":"59","author":"Lindner","year":"2018","journal-title":"J Nucl Med Off Publication Soc Nucl Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00345-8","article-title":"The foundations of immune checkpoint blockade and the ipilimumab approval decennial","volume":"21","author":"Korman","year":"2022","journal-title":"Nat Rev Drug Discov"},{"key":"B28","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1186\/s13045-023-01499-1","article-title":"Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy","volume":"16","author":"Cai","year":"2023","journal-title":"J Hematol Oncol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1744607\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:40:45Z","timestamp":1784785245000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1744607\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,23]]},"references-count":28,"alternative-id":["10.3389\/fimmu.2026.1744607"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1744607","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,23]]},"article-number":"1744607"}}