{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:27:02Z","timestamp":1793158022696,"version":"4.5.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T00:00:00Z","timestamp":1612828800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T00:00:00Z","timestamp":1612828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Nanobiotechnol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Although immunotherapy has revolutionized treatment strategies for some types of cancers, most patients failed to respond or obtain long-term benefit. Tumor-infiltrating CD8<jats:sup>+<\/jats:sup> T lymphocytes are closely related to the treatment outcome and prognosis of patients. Therefore, noninvasive elucidation of both systemic and tumor-infiltrating CD8<jats:sup>+<\/jats:sup> T lymphocytes is of extraordinary significance for patients during cancer immunotherapy. Herein, a panel of <jats:sup>68<\/jats:sup>Ga-labeled Nanobodies were designed and investigated to track human CD8<jats:sup>+<\/jats:sup> T cells in vivo through immuno-positron emission tomography (immunoPET).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Among the screened Nanobodies, SNA006a showed the highest binding affinity and specificity to both human CD8 protein and CD8<jats:sup>+<\/jats:sup> cells in vitro, with the equilibrium dissociation constant (<jats:italic>K<\/jats:italic><jats:sub><jats:italic>D<\/jats:italic><\/jats:sub>) of 6.4\u2009\u00d7\u200910<jats:sup>\u221210<\/jats:sup> M and 4.6\u2009\u00d7\u200910<jats:sup>\u221210<\/jats:sup> M, respectively. <jats:sup>68<\/jats:sup>Ga-NOTA-SNA006 was obtained with high radiochemical yield and purity, and stayed stable for at least 1\u00a0h both in vitro and in vivo. Biodistribution and Micro-PET\/CT imaging studies revealed that all tracers specifically concentrated in the CD8<jats:sup>+<\/jats:sup> tumors with low accumulation in CD8<jats:sup>\u2212<\/jats:sup> tumors and normal organs except the kidneys, where the tracer was excreted and reabsorbed. Notably, the high uptake of <jats:sup>68<\/jats:sup>Ga-NOTA-SNA006a in CD8<jats:sup>+<\/jats:sup> tumors was rapid and persistent, which reached 24.41\u2009\u00b1\u20091.00% ID\/g at 1.5\u00a0h after intravenous injection, resulting in excellent target-to-background ratios (TBRs). More specifically, the tumor-to-muscle, tumor-to-liver, and CD8<jats:sup>+<\/jats:sup> to CD8<jats:sup>\u2212<\/jats:sup> tumor was 28.10\u2009\u00b1\u20093.68, 5.26\u2009\u00b1\u20090.86, and 19.58\u2009\u00b1\u20092.70 at 1.5\u00a0h, respectively. Furthermore, in the humanized PBMC-NSG and HSC-NPG mouse models, <jats:sup>68<\/jats:sup>Ga-NOTA-SNA006a accumulated in both CD8<jats:sup>+<\/jats:sup> tumors and specific tissues such as liver, spleen and lung where human CD8 antigen was overexpressed or CD8<jats:sup>+<\/jats:sup> T cells located during immunoPET imaging.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p><jats:sup>68<\/jats:sup>Ga-NOTA-SNA006a, a novel Nanobody tracer targeting human CD8 antigen, was developed with high radiochemical purity and high affinity. Compared with other candidates, the long retention time, low background, excellent TBRs of <jats:sup>68<\/jats:sup>Ga-NOTA-SNA006a make it precisely track the human CD8<jats:sup>+<\/jats:sup> T cells in mice models, showing great potential for immunotherapy monitoring and efficacy evaluation.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12951-021-00785-9","type":"journal-article","created":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T11:10:35Z","timestamp":1612869035000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["ImmunoPET imaging of human CD8+ T cells with novel 68Ga-labeled nanobody companion diagnostic agents"],"prefix":"10.1186","volume":"19","author":[{"given":"Haitao","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijun","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangrong","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianghua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,9]]},"reference":[{"issue":"6","key":"785_CR1","doi-asserted-by":"publisher","first-page":"8509","DOI":"10.1002\/jcp.27782","volume":"234","author":"B Farhood","year":"2019","unstructured":"Farhood B, Najafi M, Mortezaee K. 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