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The sentinel lymph node (SLN) mapping can potentially enhance patient selection for lateral pelvic lymph node dissection. The current mapping agent, indocyanine green dye cannot be externally imaged prior to surgery and is not retained after entering the SLN. This study evaluated the ability of tilmanocept, a receptor-specific SLN mapping agent, to provide preoperative PET cross-sectional imaging and sustained intraoperative fluorescence images during rectal cancer surgery. Tilmanocept was labeled with gallium-68, technetium-99m, and a near-infrared fluorophore. Four pigs were studied. Tilmanocept was injected into the submucosal layer of the rectal wall followed 1\u00a0h later by PET\/CT images of the pelvis, which identified ten SLNs, one of which was a pudendal artery regional SLN. Approximately 45\u00a0h after administration, SLN dissection was guided by fluorescence imaging during robotic surgery. The tenth SLN was excised by open surgery. The radioactive and fluorescent intensities of all ten excised SLNs were significantly higher than the non-SLNs. The ability of dual-labeled tilmanocept to provide preoperative SLN imaging can potentially reduce morbidity and operation time by identifying patients who will not require lateral pelvic lymph node dissections.<\/jats:p>","DOI":"10.1038\/s41598-025-21160-w","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T13:45:10Z","timestamp":1761572710000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multimodal tilmanocept for preoperative imaging and fluorescence-guided surgery of porcine lateral pelvic sentinel lymph nodes"],"prefix":"10.1038","volume":"15","author":[{"given":"Ryotaro","family":"Ogawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junichiro","family":"Kawamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward T.","family":"Ashworth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo Bin","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Hall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatoshi","family":"Kudo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl K.","family":"Hoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Vera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"21160_CR1","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1007\/s11605-017-3427-9","volume":"21","author":"S Dayal","year":"2017","unstructured":"Dayal, S., Battersby, N. & Cecil, T. 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