中国癌症杂志 ›› 2021, Vol. 31 ›› Issue (10): 873-878.doi: 10.19401/j.cnki.1007-3639.2021.10.001

• 专家述评 • 上一篇    下一篇

乳腺癌前哨淋巴结活检光声示踪剂的进展与展望

赵家贤 1,2 ,王春建 1,2 ,丛斌斌 1,2 ,王永胜 1,2   

  1. 1. 山东第一医科大学(山东省医学科学院),山东 济南 250062 ;
    2. 山东省肿瘤防治研究院(山东省肿瘤医院)乳腺病中心,山东 济南 250117
  • 出版日期:2021-10-30 发布日期:2021-11-08
  • 通信作者: 王永胜 E-mail: wangysh2008@aliyun.com

Research progress of photoacoustic imaging in sentinel lymph node biopsy in breast cancer

ZHAO Jiaxian 1,2 , WANG Chunjian 1,2 , CONG Binbin 1,2 , WANG Yongsheng 1,2   

  1. 1. Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250062, Shandong Province, China; 2. Breast Cancer Center, Shandong Cancer Hospital and Institute, Jinan 250117, Shandong Province, China
  • Published:2021-10-30 Online:2021-11-08
  • Contact: WANG Yongsheng E-mail: wangysh2008@aliyun.com

摘要: 乳腺癌是女性最常见的恶性肿瘤,其发病率呈逐年上升趋势。区域淋巴结转移状况是乳腺癌重要的预后指标,乳腺癌腋窝前哨淋巴结活检(sentinel lymph node biopsy,SLNB)已代替腋窝淋巴结清扫成为早期乳腺癌患者明确区域淋巴结转移情况的标准方法,目前指南推荐蓝染法联合核素法作为标准的前哨淋巴结(sentinel lymph node,SLN)示踪方法。示踪剂的选择是进行乳腺癌SLNB研究的关键环节,理想的SLN示踪剂应具备可视性、靶向性及可重复性,同时需要有循证医学证据支持、操作便捷、价格低廉和不良反应轻等特点。当前示踪剂大致可分为可视类示踪剂和造影类示踪剂,前者包括菁染料如亚甲蓝,碳纳米材料如碳纳米悬浮液,示踪用米托蒽醌等;后者包括核素,荧光示踪剂如吲哚菁绿,磁性示踪剂如超顺磁性氧化铁,超声造影剂如六氟化硫微泡等。以上示踪剂均有一定局限性,如亚甲蓝缺乏靶向性,吲哚菁绿的荧光穿透组织厚度低,核素具有放射性污染等。为此,许多研究围绕乳腺癌SLN新型示踪剂的研发及改良进行。光声成像(photoacoustic imaging,PAI)是利用光声效应成像的新型影像技术,生物内源性生色基团或外源性造影剂吸收脉冲光引起局部热弹性膨胀,随后向外辐射超声波,由于不同组织成分的光吸收系数不同,超声换能器可以检测到不同强度的超声波,分析处理后可形成生物组织光能吸收差异分布图,即成像,具有光学成像高对比度和超声成像高穿透力的优势。PAI技术通过光声造影剂及其偶联基团可对标记组织进行形态显像及功能评估,光声造影剂通过改变生物组织局部的声学和光学特性,来提高PAI分辨率和对比度,从而增强PAI的成像效果并获取一定的光声信息。SLN示踪剂中小分子近红外染料、金属纳米材料、碳纳米材料均在PAI领域中广泛应用,是一种乳腺癌SLN新型示踪方法,可避免放射性损伤。本文对PAI及其造影剂在乳腺癌SLNB中的应用研究进展进行综述,重点探讨以小分子近红外染料、贵金属纳米材料、碳纳米材料为代表的光声造影剂作为乳腺癌SLN示踪剂的应用现状,并展望未来的发展前景。

关键词: 光声成像, 前哨淋巴结活检, 光声示踪剂

Abstract: Breast cancer is the most common malignant tumor in women, and its incidence is increasing year by year. Regional lymph node metastasis status is an important prognostic indicator of breast cancer. Sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) as the standard method to identify regional lymph node metastasis in early-stage breast cancer patients. The current guidelines recommend blue dye and nuclear methods as the standard sentinel lymph node (SLN) tracing methods. The ideal SLN tracer should be visualized, targeted and reproducible, supported by evidence-based medical evidence, easy to use and inexpensive with minimal adverse effects. Currently, the tracers can be broadly divided into visual tracers and contrast tracers, with the former including cyanine dyes such as methylene blue, carbon nanomaterials such as carbon nanosuspensions, and mitoxantrone for tracing; the latter including nucleophiles, fluorescent tracers such as indocyanine green, magnetic tracers such as superparamagnetic iron oxide, and ultrasound contrast agents such as sulfur hexafluoride microbubbles. All these tracers have certain limitations, such as lack of targeting of methylene blue, low fluorescence penetration of indocyanine green, and radioactive contamination of nucleophiles. For this reason, many studies have been conducted on the development and improvement of new tracers for SLN of breast cancer. Photoacoustic imaging (PAI) is a new imaging technique utilizing photoacoustic effect, in which biological endogenous chromophores or exogenous contrast agents absorb pulsed light to cause local thermoelastic expansion and subsequently radiate ultrasonic waves outward, forming a biological tissue light energy absorption difference distribution map and imaging. The PAI technique can be used to evaluate the morphology and function of labeled tissues through photoacoustic contrast agents and their coupling groups. In this paper, we reviewed the progress of PAI and its contrast agent application in SLNB, focusing on the small molecule NIR dyes, metallic nanomaterials and carbon nanomaterials. At the same time, we discussed the research of new targeted fluorescent tracer formed after combining small molecule near-infrared dyes with molecular antibodies as a common ligand. At last, we presented the future perspectives in this field.

Key words: Photoacoustic imaging, Sentinel lymph node biopsy, Photoacoustic contrast agent