吲哚青绿
医学
手术切缘
触诊
乳腺癌
体内
病理
癌症
外科
切除术
生物
内科学
生物技术
作者
Masahide Goto,Ingeun Ryoo,Samer A Naffouje,Sunam Mander,Konstantin Christov,Jing Wang,Albert Green,Anne Shilkaitis,Tapas K. Das Gupta,Tohru Yamada
出处
期刊:EBioMedicine
[Elsevier]
日期:2022-02-01
卷期号:76: 103850-103850
被引量:4
标识
DOI:10.1016/j.ebiom.2022.103850
摘要
Given the lack of visual discrepancy between malignant and surrounding normal tissue, current breast conserving surgery (BCS) is associated with a high re-excision rate. Due to the increasing cases of BCS, a novel method of complete tumour removal at the initial surgical resection is critically needed in the operating room to help optimize the surgical procedure and to confirm tumour-free edges.We developed a unique near-infrared (NIR) fluorescence imaging probe, ICG-p28, composed of the clinically nontoxic tumour-targeting peptide p28 and the FDA-approved NIR dye indocyanine green (ICG). ICG-p28 was characterized in vitro and evaluated in multiple breast cancer animal models with appropriate control probes. Our experimental approach with multiple-validations and -blinded procedures was designed to determine whether ICG-p28 can accurately identify tumour margins in mimicked intraoperative settings.The in vivo kinetics were analysed to optimize settings for potential clinical use. Xenograft tumours stably expressing iRFP as a tumour marker showed significant colocalization with ICG-p28, but not ICG alone. Image-guided surgery with ICG-p28 showed an over 6.6 × 103-fold reduction in residual normalized tumour DNA at the margin site relative to control approaches (i.e., surgery with ICG or palpation/visible inspection alone), resulting in an improved tumour recurrence rate (92% specificity) in multiple breast cancer animal models independent of the receptor expression status. ICG-p28 allowed accurate identification of tumour cells in the margin to increase the complete resection rate.Our simple and cost-effective approach has translational potential and offers a new surgical procedure that enables surgeons to intraoperatively identify tumour margins in a real-time, 3D fashion and that notably improves overall outcomes by reducing re-excision rates.This work was supported by NIH/ National Institute of Biomedical Imaging and Bioengineering, R01EB023924.
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