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Transl. Med."],"published-print":{"date-parts":[[2026,10,21]]},"abstract":"<jats:p>\n                    Choline kinase \u03b1 (ChoK\u03b1) is a biomarker of lung cancer, is overexpressed in 60% of human pulmonary malignancies, and is associated with an aggressive phenotype and poor clinical outcome. Patients with lung cancer who undergo surgery have a recurrence rate of 30 to 50%, indicating a potential need for better tumor detection modalities. A near-infrared fluorescent ChoK\u03b1-targeting imaging agent, JAS239 (\u03bb\n                    <jats:sub>ex<\/jats:sub>\n                    , \u03bb\n                    <jats:sub>em<\/jats:sub>\n                    : 745, 775 nanometers), was developed for intraoperative identification of tumors, their margins, and local metastases. In lung cancer cells, JAS239 inhibited phosphocholine production, reduced viability in a dose-dependent manner, and accumulated in the cytoplasm where ChoK\u03b1 is active. JAS239 had favorable pharmacokinetics and pharmacodynamics for imaging metastatic lung lesions in mice. In situ and ex vivo fluorescence imaging of primary lung tumors in a canine clinical trial showed distinct tumor identification and margin delineation with a tumor-to-background ratio of 5.0\u00a0\u00b1\u00a00.6 and a contrast-to-variance ratio of 2.0\u00a0\u00b1\u00a00.2 at 0.5 milligram\/kilogram. Fluorescence imaging identified a clinically significant event where an occult lesion was found after primary tumor resection. Fluorescence imaging also identified a close surgical margin, which prompted further investigation. Immunohistochemistry for ChoK\u03b1 showed overexpression in canine lung tumors proportional to tumor fluorescence. Ex vivo human tumor painting demonstrated preferential JAS239 localization with a tumor-to-background ratio of 1.5\u00a0\u00b1\u00a00.1 and a contrast-to-variance ratio of 0.9\u00a0\u00b1\u00a00.1. These studies establish JAS239 as a safe and effective imaging agent for intraoperative lung tumor detection, warranting further evaluation for human patients with lung cancer.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.aea4947","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:58:57Z","timestamp":1792605537000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["A fluorescent choline kinase alpha inhibitor for intraoperative molecular imaging during resection of canine NSCLC tumors"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1545-2697","authenticated-orcid":true,"given":"Sofya A.","family":"Osharovich","sequence":"first","affiliation":[{"name":"Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, 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