Fast and Durable Intraoperative Near‐infrared Imaging of Ovarian Cancer Using Ultrabright Squaraine Fluorophores
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- Takeshi Fukuda
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital and Harvard Medical School Boston MA 02114 USA
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- Shinya Yokomizo
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital and Harvard Medical School Boston MA 02114 USA
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- Stefanie Casa
- Department of Chemistry Georgia State University Atlanta GA 30303 USA
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- Hailey Monaco
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital and Harvard Medical School Boston MA 02114 USA
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- Sophia Manganiello
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital and Harvard Medical School Boston MA 02114 USA
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- Haoran Wang
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital and Harvard Medical School Boston MA 02114 USA
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- Xiangmin Lv
- Vincent Center for Reproductive Biology Vincent Department of Obstetrics and Gynecology Massachusetts General Hospital Boston MA 02114 USA
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- Amy Daniel Ulumben
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital and Harvard Medical School Boston MA 02114 USA
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- Chengeng Yang
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital and Harvard Medical School Boston MA 02114 USA
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- Min‐Woong Kang
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital and Harvard Medical School Boston MA 02114 USA
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- Kazumasa Inoue
- Department of Radiological Sciences Tokyo Metropolitan University 7-2-10 Higashi-Ogu, Arakawa Tokyo 116-8551 Japan
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- Masahiro Fukushi
- Department of Radiological Sciences Tokyo Metropolitan University 7-2-10 Higashi-Ogu, Arakawa Tokyo 116-8551 Japan
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- Toshiyuki Sumi
- Department of Obstetrics and Gynecology Osaka City University Graduate School of Medicine 1-4-3, Asahimachi, Abeno-ku Osaka 545-8585 Japan
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- Cheng Wang
- Vincent Center for Reproductive Biology Vincent Department of Obstetrics and Gynecology Massachusetts General Hospital Boston MA 02114 USA
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- Homan Kang
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital and Harvard Medical School Boston MA 02114 USA
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- Kai Bao
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital and Harvard Medical School Boston MA 02114 USA
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- Maged Henary
- Department of Chemistry Georgia State University Atlanta GA 30303 USA
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- Satoshi Kashiwagi
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital and Harvard Medical School Boston MA 02114 USA
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- Hak Soo Choi
- Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital and Harvard Medical School Boston MA 02114 USA
抄録
<jats:title>Abstract</jats:title><jats:p>The residual tumor after surgery is the most significant prognostic factor of patients with epithelial ovarian cancer. Near‐infrared (NIR) fluorescence‐guided surgery is actively utilized for tumor localization and complete resection during surgery. However, currently available contrast‐enhancing agents display low on‐target binding, unfavorable pharmacokinetics, and toxicity, thus not ideal for clinical use. Here we report ultrabright and stable squaraine fluorophores with optimal pharmacokinetics by introducing an asymmetric molecular conformation and surface charges for rapid transporter‐mediated cellular uptake. Among the tested, OCTL14 shows low serum binding and rapid distribution into cancer tissue via organic cation transporters (OCTs). Additionally, the charged squaraine fluorophores are retained in lysosomes, providing durable intraoperative imaging in a preclinical murine model of ovarian cancer up to 24 h post‐injection. OCTL14 represents a significant departure from the current bioconjugation approach of using a non‐targeted fluorophore and would provide surgeons with an indispensable tool to achieve optimal resection.</jats:p>
収録刊行物
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- Angewandte Chemie International Edition
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Angewandte Chemie International Edition 61 (17), 2022-02-26
Wiley