Brain metastasis is the most common intracranial malignancy in adults. The prognosis is extremely poor, partly because most patients have more than one brain lesion, and the currently available therapies are nonspecific or inaccessible to those occult metastases due to an impermeable blood–tumor barrier (BTB). Phosphatidylserine (PS) is externalized on the surface of viable endothelial cells (ECs) in tumor blood vessels. In this study, we have applied a PS-targeting antibody to assess brain metastases in mouse models. Fluorescence microscopic imaging revealed that extensive PS exposure was found exclusively on vascular ECs of brain metastases. The highly sensitive and specific binding of the PS antibody enables individual metastases, even micrometastases containing an intact BTB, to be clearly delineated. Furthermore, the conjugation of the PS antibody with a fluorescence dye, IRDye 800CW, or a radioisotope,125I, allowed the clear visualization of individual brain metastases by optical imaging and autoradiography, respectively. In conclusion, we demonstrated a novel strategy for targeting brain metastases based on our finding that abundant PS exposure occurs on blood vessels of brain metastases but not on normal brain, which may be useful for the development of imaging and targeted therapeutics for brain metastases.
脑转移是成人最常见的颅内恶性肿瘤，其预后极差，部分原因在于多数患者存在多发性脑部病灶，且现有疗法因血瘤屏障（BTB）的不可渗透性而无法作用于隐匿性转移灶。在肿瘤血管系统中，磷脂酰丝氨酸（PS）会外化表达于存活内皮细胞（ECs）表面。本研究采用靶向PS的抗体评估小鼠模型中的脑转移情况。荧光显微成像显示，PS广泛暴露仅见于脑转移灶的血管内皮细胞。该PS抗体具有高度敏感性和特异性结合能力，能清晰勾勒出单个转移灶（甚至包含完整血瘤屏障的微转移灶）的边界。此外，将PS抗体与荧光染料IRDye 800CW或放射性同位素125I偶联后，分别通过光学成像和放射自显影技术实现了单个脑转移灶的清晰可视化。综上所述，基于脑转移灶血管（而非正常脑组织）存在大量PS暴露这一发现，我们提出了一种靶向脑转移的新策略，该策略可能为脑转移的影像学诊断和靶向治疗开发提供新途径。
肿瘤(癌症)患者之家