Image-guided surgery with a new tumour-targeting probe improves the identification of positive margins.
Image-guided surgery with a new tumour-targeting probe improves the identification of positive margins.
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DOI：
10.1016/j.ebiom.2022.103850
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发表时间：
2022-03
期刊：
影响因子：
11.1
通讯作者：
Yamada T
中科院分区：
文献类型：
--
作者：
Goto M;Ryoo I;Naffouje S;Mander S;Christov K;Wang J;Green A;Shilkaitis A;Das Gupta TK;Yamada T
鉴于恶性和周围正常组织之间缺乏视觉差异，目前的保乳手术（BCS）与高再切除率相关。由于BCS病例的增加，手术室迫切需要一种新的在初始手术切除时完全切除肿瘤的方法，以帮助优化手术过程并确认无肿瘤边缘。我们开发了一种独特的近红外（NIR）荧光成像探针，ICG-p28，由临床无毒的肿瘤靶向肽p28和fda批准的近红外染料吲哚菁绿（ICG）组成。采用适当的对照探针对ICG-p28进行体外表征，并在多种乳腺癌动物模型中进行评价。我们的实验方法采用多重验证和盲法程序，旨在确定ICG-p28是否可以在模拟术中环境中准确识别肿瘤边缘。体内动力学分析，以优化设置为潜在的临床应用。稳定表达iRFP作为肿瘤标志物的异种移植物肿瘤显示出与ICG-p28的显著共定位，但不单独表达ICG。图像引导下的ICG-p28手术显示，与对照方法（即ICG手术或单独触诊/可见检查）相比，边缘部位残留的归一化肿瘤DNA减少了6.6 × 103倍以上，从而在独立于受体表达状态的多种乳腺癌动物模型中提高了肿瘤复发率（92%特异性）。ICG-p28可以准确识别边缘的肿瘤细胞，提高完全切除率。我们的方法简单且具有成本效益，具有转化潜力，并提供了一种新的外科手术方法，使外科医生能够在术中实时、3D地识别肿瘤边缘，并通过降低再切除率显着改善总体结果。这项工作得到了NIH/国家生物医学成像和生物工程研究所的支持，编号为R01EB023924。
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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影响因子：
12.4
作者：
Blau R;Epshtein Y;Pisarevsky E;Tiram G;Israeli Dangoor S;Yeini E;Krivitsky A;Eldar-Boock A;Ben-Shushan D;Gibori H;Scomparin A;Green O;Ben-Nun Y;Merquiol E;Doron H;Blum G;Erez N;Grossman R;Ram Z;Shabat D;Satchi-Fainaro R
通讯作者：
Satchi-Fainaro R
用于甲状旁腺和甲状腺成像的近红外荧光团的结构固有靶向。
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
4.3
作者：
Hock, Andreas K.;Lee, Pearl;Vousden, Karen H.
通讯作者：
Vousden, Karen H.
DOI：
10.1073/pnas.1513433112
发表时间：
2015-08-18
影响因子：
11.1
作者：
Lu, Haiquan;Samanta, Debangshu;Semenza, Gregg L.
通讯作者：
Semenza, Gregg L.
影响因子：
254.7
作者：
Giuliano, Armando E.;Connolly, James L.;Hortobagyi, Gabriel N.
通讯作者：
Hortobagyi, Gabriel N.