Noninvasive monitoring of liver metastasis development via combined multispectral photoacoustic imaging and fluorescence diffuse optical tomography
Noninvasive monitoring of liver metastasis development via combined multispectral photoacoustic imaging and fluorescence diffuse optical tomography
复制标题
多光谱光声成像和荧光扩散光学断层成像联合无创监测肝转移瘤的进展
DOI：
10.7150/ijbs.40896
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发表时间：
2020-01-01
影响因子：
9.2
通讯作者：
Josserand, Veronique
中科院分区：
文献类型：
--
作者：
Lavaud, Jonathan;Henry, Maxime;Josserand, Veronique
原理：临床前动物模型的体内分子成像是了解癌症发展过程中涉及的病理生理机制和进行药物开发研究的首选工具。此外，结合多种成像方式可以提供多方面，互补和交叉验证的信息。光声成像（PAI）是一种很有前途的成像方式，可以反映血管和组织氧合以及检测外源性分子，但PAI的一个缺点是缺乏能够提供肿瘤对比的有机光声造影剂。方法：建立结肠癌肝转移动物模型，利用体内生物发光和x线微计算机断层扫描监测转移的进展。无造影剂PAI用于检测氧和脱氧血红蛋白的各自量，从而检测肝组织氧合。两种造影剂Angiostamp800和吲哚花青素绿（ICG）分别具有和不具有肿瘤靶向特异性，然后评估其双荧光和光声可探测性，然后在不同疾病发展阶段用于联合PAI和荧光漫射光学断层扫描（fDOT）。结果：无造影剂PAI反映了肿瘤在转移发展过程中的血管生成和逐渐缺氧。多光谱PAI能够无创实时监测ICG血药代动力学，显示肿瘤相关的肝功能障碍。PAI和荧光ICG信号在有转移的肝脏中明显改变，但不能区分不同的疾病分期。相比之下，使用肿瘤特异性标记物Angiostamp800，在转移发展过程中提供逐渐增加的PAI和fDOT信号，取得了显著的改善。结论：我们首次证明了Angiostamp800作为双峰肿瘤靶向造影剂在体内联合PAI和肝转移进展的荧光成像中的价值。
Rationale: In vivo molecular imaging in preclinical animal models is a tool of choice for understanding the pathophysiological mechanisms involved in cancer development and for conducting drug development research. Moreover, combining several imaging modalities can provide multifaceted, complementary and cross-validated information. Photoacoustic imaging (PAI) is a promising imaging modality that can reflect blood vasculature and tissue oxygenation as well as detect exogenous molecules, but one shortcoming of PAI is a lack of organic photoacoustic contrast agents capable of providing tumor contrast.Methods: In the present study, we designed an animal model of liver metastases from colon cancer and monitored metastasis development by in vivo bioluminescence and X-ray microcomputed tomography. Contrast-agent-free PAI was used to detect the respective amounts of oxy- and deoxyhemoglobin and, thus, liver tissue oxygenation. two contrast agents, Angiostamp800 and indocyanin green (ICG), respectively with and without tumor targeting specificity, were then evaluated for their dual fluorescence and photoacoustic detectability and were then used for combined PAI and fluorescence diffuse optical tomography (fDOT) at various disease development stages.Findings: Contrast-agent-free PAI reflected tumor angiogenesis and gradual hypoxia during metastasis development. Multispectral PAI enabled noninvasive real-time monitoring of ICG blood pharmacokinetics, which demonstrated tumor-related liver dysfunction. Both PAI and fluorescence ICG signals were clearly modified in metastasis-bearing livers but did not allow for differentiation between different disease stages. In contrast, there was a significant improvement achieved by using the tumor-specific marker Angiostamp800, which provided gradually increasing PAI and fDOT signals during metastasis development.Conclusion: We demonstrated for the first time the value of using Angiostamp800 as a bimodal tumor-targeting contrast agent for combined PAI and fluorescence imaging of liver metastasis progression in vivo.