Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way, Cambridge, CB2 0RE, UK.
Department of Physics, University of Cambridge, Cambridge, UK.
Breast Cancer Res. 2021 Feb 17;23(1):25. doi: 10.1186/s13058-021-01404-z.
Ductal carcinoma in situ (DCIS) is a non-invasive form of early breast cancer, with a poorly understood natural history of invasive transformation. Necrosis is a well-recognized adverse prognostic feature of DCIS, and non-invasive detection of its presence and spatial extent could provide information not obtainable by biopsy. We describe here imaging of the distribution and extent of comedo-type necrosis in a model of human DCIS using C2Am, an imaging agent that binds to the phosphatidylserine exposed by necrotic cells.
We used an established xenograft model of human DCIS that mimics the histopathological features of the disease. Planar near-infrared and optoacoustic imaging, using fluorescently labeled C2Am, were used to image non-invasively the presence and extent of lesion necrosis.
C2Am showed specific and sensitive binding to necrotic areas in DCIS tissue, detectable both in vivo and ex vivo. The imaging signal generated in vivo using near-infrared (NIR) fluorescence imaging was up to 6-fold higher in DCIS lesions than in surrounding fat pad or skin tissue. There was a correlation between the C2Am NIR fluorescence (Pearson R = 0.783, P = 0.0125) and optoacoustic signals (R > 0.875, P < 0.022) in the DCIS lesions in vivo and the corresponding levels of cell death detected histologically.
C2Am is a targeted multi-modal imaging agent that could complement current anatomical imaging methods for detecting DCIS. Imaging the presence and spatial extent of necrosis may give better prognostic information than that obtained by biopsy alone.
导管原位癌（DCIS）是一种非浸润性早期乳腺癌，其浸润性转化的自然史尚不清楚。坏死是 DCIS 的一个公认的不良预后特征，非侵入性地检测其存在和空间范围可以提供通过活检无法获得的信息。我们在这里描述了使用 C2Am 对人类 DCIS 模型中粉刺型坏死的分布和范围进行成像的情况，C2Am 是一种与坏死细胞暴露的磷脂酰丝氨酸结合的成像剂。
我们使用了一种已建立的人 DCIS 异种移植模型，该模型模拟了该疾病的组织病理学特征。使用荧光标记的 C2Am 进行近红外和光声成像，以非侵入性地检测病变坏死的存在和范围。
C2Am 对 DCIS 组织中的坏死区域具有特异性和敏感性，无论是在体内还是在体外观测均可检测到。使用近红外（NIR）荧光成像在体内产生的成像信号在 DCIS 病变中比周围的脂肪垫或皮肤组织高 6 倍。C2Am 的 NIR 荧光（Pearson R = 0.783，P = 0.0125）与体内 DCIS 病变的光声信号（R > 0.875，P < 0.022）之间存在相关性，以及组织学上检测到的细胞死亡水平。
C2Am 是一种靶向多模态成像剂，可补充当前用于检测 DCIS 的解剖成像方法。成像坏死的存在和空间范围可能比单独活检获得的预后信息更好。
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