{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:19:24Z","timestamp":1790072364073,"version":"4.0.1"},"reference-count":48,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"19","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA266701"],"award-info":[{"award-number":["R01 CA266701"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 CA084203"],"award-info":[{"award-number":["P01 CA084203"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA231606"],"award-info":[{"award-number":["R01 CA231606"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10 OD012326"],"award-info":[{"award-number":["S10 OD012326"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 CA279862"],"award-info":[{"award-number":["U01 CA279862"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,5,8]]},"abstract":"<jats:p>Molecular fluorescence imaging is effective for tumor diagnosis but limited by low-depth profiling, which can be addressed by photoacoustic (PA) imaging. However, PA imaging has low sensitivity due to microenvironment-induced effects on exogenous contrast agents. Accordingly, the temporal and biophysical determinants of PA contrast in Cetuximab-IRDye800 conjugates should be performed to complement fluorescence-based diagnostics. In this study, we compare the temporal dynamics of PA and fluorescence signals from a Cetuximab-IRDye800 conjugate in a tumor xenograft model. We demonstrate that while fluorescence signal increases steadily over time after administration of Cetuximab-IRDye800, PA signal peaks early (~75% higher at 3 hours), followed by a decrease (~24% higher at 24 hours). Mechanistic analysis revealed formation of H-aggregates with Cetuximab-IRDye800 conjugation, which results in enhanced PA contrast, while receptor-mediated endocytosis disrupts these aggregates, reducing PA signal intensity over time. These findings underscore the complementary nature of PA and fluorescence imaging and emphasize timing as a critical factor for capturing peak PA contrast for tumor diagnostics.<\/jats:p>","DOI":"10.1126\/sciadv.adv4639","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T17:59:26Z","timestamp":1778090366000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Contrasting temporal dynamics of fluorescence and photoacoustic signals from Cetuximab-IRDye800 conjugate in EGFR-overexpressing tumors"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3337-2076","authenticated-orcid":true,"given":"Mohammad A.","family":"Saad","sequence":"first","affiliation":[{"name":"Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6831-1140","authenticated-orcid":true,"given":"Derek","family":"Allen","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8909-8001","authenticated-orcid":true,"given":"Allison","family":"Sweeney","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Science and Technology Center, Tufts University, Medford, MA 02155, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8361-7318","authenticated-orcid":true,"given":"Marvin","family":"Xavierselvan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Science and Technology Center, Tufts University, Medford, MA 02155, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1547-1764","authenticated-orcid":true,"given":"Srivalleesha","family":"Mallidi","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA."},{"name":"Department of Biomedical Engineering, Science and Technology Center, Tufts University, Medford, MA 02155, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0871-6057","authenticated-orcid":true,"given":"Tayyaba","family":"Hasan","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA."},{"name":"Division of Health Sciences and Technology, Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02139, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44222-022-00017-1"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2004.07.007"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbio.202300105"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyp135"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-009-0594-2"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2000.93.6.1003"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","unstructured":"P. Ferroli F. Acerbi E. Albanese G. Tringali M. Broggi A. Franzini G. Broggi \u201cApplication of intraoperative indocyanine green angiography for CNS tumors: Results on the first 100 cases \u201d in Intraoperative Imaging M. N. Pamir V. Seifert T. Kiris Eds. (Springer 2011) pp. 251\u2013257.","DOI":"10.1007\/978-3-211-99651-5_40"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-3598"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1117\/1.JBO.22.12.121607"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1319493111"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.17.7973"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-3284"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30600-8"},{"key":"e_1_3_2_15_2","article-title":"Dual in vivo photoacoustic and fluorescence imaging of HER2 expression in breast tumors for diagnosis, margin assessment, and surgical guidance","volume":"13","author":"Maeda A.","year":"2014","unstructured":"A. Maeda, J. Bu, J. Chen, G. Zheng, R. S. DaCosta, Dual in vivo photoacoustic and fluorescence imaging of HER2 expression in breast tumors for diagnosis, margin assessment, and surgical guidance. Mol. Imaging 13, 10.2310\/7290.2014.00043 (2014).","journal-title":"Mol. Imaging"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/s141019660"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/bc5003983"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44222-024-00240-y"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.120.245241"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.18217"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-023-08073-y"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pacs.2022.100362"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(20)30088-1"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2020.05.022"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.133.5.511"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.otohns.2007.06.736"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejso.2009.10.014"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nnano.2014.130"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25452-3"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.bioconjchem.3c00406"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.2c00260"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11307-014-0773-9"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1609"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-3717"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-20-0033"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dyepig.2016.03.054"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/lary.29891"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/php.13501"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032241"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1021\/bc100457s"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201203427"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.5b05576"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pacs.2017.12.001"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19498-y"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.853660"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.4c00046"},{"key":"e_1_3_2_47_2","first-page":"20170262","article-title":"Spectral unmixing techniques for optoacoustic imaging of tissue pathophysiology","volume":"375","author":"Tzoumas S.","year":"2017","unstructured":"S. Tzoumas, V. Ntziachristos, Spectral unmixing techniques for optoacoustic imaging of tissue pathophysiology. Philos. Trans. A Math. Phys. Eng. Sci 375, 20170262 (2017).","journal-title":"Philos. Trans. A Math. Phys. Eng. Sci"},{"key":"e_1_3_2_48_2","unstructured":"S. A. Prahl Optical absorption of hemoglobin (1999); https:\/\/omlc.org\/spectra\/hemoglobin\/."},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend-1-3-216"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adv4639","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T18:03:59Z","timestamp":1778090639000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adv4639"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":48,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2026,5,8]]}},"alternative-id":["10.1126\/sciadv.adv4639"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adv4639","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,8]]},"assertion":[{"value":"2025-01-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadv4639"}}