Graduate School of Biomedical Engineering, Tohoku University, Sendai, Miyagi, Japan.
Cancer Res. 2011 Nov 15;71(22):6957-64. doi: 10.1158/0008-5472.CAN-11-2389. Epub 2011 Oct 7.
Acoustic liposomes (AL) have their inherent echogenicity and can add functionality in serving as drug carriers with tissue specificity. Nonuniform vascular structures and vascular branches/bends are evaluated by imaging the intravascular movement locus of ALs with high-frequency ultrasound (HF-US) imaging. However, the evaluation of antitumor effects on angiogenesis by ALs and HF-US imaging has not been reported. Here, we show that the combination of ALs and an HF-US imaging system is capable of noninvasively evaluating antitumor volumetric and angiogenic effects in preclinical mouse models of various cancers. In this study, the antitumor effects of cisplatin on tumor growth and angiogenesis in mice bearing two different types of tumor cells were assessed. By tracking each AL flowing in the vessel and transferring the images to personal computers, microvessel structures were mapped and reconstructed using the color difference based on SD method. The antitumor effects were confirmed with an in vivo bioluminescence imaging system and immunohistochemical analysis. Our results show that cisplatin inhibits tumor growth by decreasing intratumoral vessel area but does not affect the angiogenesis ratio in the tumor. The vascular occupancy in the outer region of the tumor was larger than that in the inner region; however, both occupancies were similar to those of the control tumor. We propose that this method of mapping microvessels with ALs and an HF-US system can serve as a new molecular imaging method for the assessment of angiogenesis and can be applied to evaluate the antitumor effects by various therapeutic agents.
声敏脂质体（AL）具有固有回声性，并且可以作为具有组织特异性的药物载体增加功能。通过高频超声（HF-US）成像来评估血管内 AL 的血管内运动轨迹，从而评估不均匀的血管结构和血管分支/弯曲。但是，尚未有报道使用 AL 和 HF-US 成像来评估抗肿瘤作用对血管生成的影响。在这里，我们证明了 AL 和 HF-US 成像系统的组合能够在各种癌症的临床前小鼠模型中对肿瘤体积和血管生成的抗肿瘤作用进行非侵入性评估。在这项研究中，评估了顺铂对携带两种不同类型肿瘤细胞的小鼠肿瘤生长和血管生成的抗肿瘤作用。通过跟踪在血管中流动的每个 AL，并将图像传输到个人计算机上，使用基于 SD 方法的色差来映射和重建微血管结构。通过体内生物发光成像系统和免疫组织化学分析来确认抗肿瘤作用。我们的结果表明，顺铂通过减少肿瘤内血管面积来抑制肿瘤生长，但不影响肿瘤中的血管生成比例。肿瘤外区域的血管占有率大于肿瘤内区域；但是，这两个占有率与对照肿瘤的占有率相似。我们提出，这种使用 AL 和 HF-US 系统绘制微血管的方法可以作为评估血管生成的新分子成像方法，并可用于评估各种治疗剂的抗肿瘤作用。
