Exploring combined hyperpolarized 13C MRI with liver-specific gadolinium contrast agents for improved metabolic assessment of liver tumors

摘要 本项目的目标是开发一种新的超极化（HP）13 C MR成像和光谱学方法 肝肿瘤的治疗，允许肿瘤代谢的靶向评估。肝脏肿瘤的代谢成像是 临床上重要的原因有几个。肝肿瘤通常采用局部区域治疗（放射， 化学或热消融），需要密切评估肿瘤反应和复发。此外，本发明还 已知在许多治疗，特别是放射疗法之后，代谢变化先于尺寸变化。HP 13 C MRI是一种有前途的新兴分子成像工具，具有许多潜在的应用于癌症 影像学检查包括肝肿瘤。然而，超极化MR信号对器官和组织类型没有特异性。 例如，在受损的肝脏中，目前不可能确定观察到的超极化信号是否 来自肝细胞或炎症细胞。同样，由于大多数图像的空间分辨率有限， 在HP MRI研究中，同样不可能将小肿瘤产生的信号与周围的信号分开。 非肿瘤肝细胞，其也具有高代谢活性。这种缺乏特异性限制了 HP 13 C MRI用于监测肝肿瘤的生存能力及其对治疗的反应。因此， 未满足的需要是增加肝肿瘤的超极化13 C MRI测量的细胞特异性。我们 建议通过将超极化13 C MRI与肝脏结合， 选择性地进入肝细胞的特定钆基造影剂。因为探员位于 在肝细胞而不是肿瘤细胞内，它将缩短T1（因此淬灭信号）， 这些化合物位于肝细胞内，并保留来自肿瘤细胞的信号（其排除了肿瘤细胞的信号）。 钆造影剂）。这项探索性研究旨在测试和证明这种方法的可行性。 approach.使用转移性结肠癌的动物模型，将进行超极化采集 在给予钆造影剂之前和之后。我们会发现造影剂的剂量和时间 注射，其最大化从肝肿瘤细胞接收的信号量，同时最小化 信号来自邻近的正常肝脏。据我们所知，这将是第一个 使用靶向特定细胞类型的钆造影剂进行超极化13 C成像。此外该 背景肝信号的抑制不可能使用竞争性分子成像技术 FDG-PET，这表明该技术可能为肝脏超极化13 C MRI创造独特的作用 肿瘤成像最后，如果这项工作是成功的，这项技术应该可以迅速转化为未来的研究 在人类身上。

Abstract The goal of this project is to develop a new method for hyperpolarized (HP) 13C MR imaging and spectroscopy of liver tumors that permits targeted evaluation of tumor metabolism. Metabolic imaging of liver tumors is clinically important for several reasons. Liver tumors are often treated with local-regional therapies (radiation, chemical or thermal ablation), requiring close evaluation for tumor response and recurrence. Additionally, metabolic changes are known to precede size changes following many treatments, especially radiotherapy. HP 13C MRI is a promising emerging molecular imaging tool for with numerous potential applications to cancer imaging including liver tumors. However, the hyperpolarized MR signal is not specific for organ and tissue type. In the injured liver, for example, it is currently impossible to determine if the observed hyperpolarized signal comes from hepatocytes or from inflammatory cells. Similarly, because of the limited spatial resolution of most HP MRI studies, it is likewise impossible to separate the signal arising from small tumors from surrounding non-tumorous hepatocytes, which also have high metabolic activity. This lack of specificity limits the potential for HP 13C MRI to monitor the viability of liver tumors and their responses to treatment. There is therefore an unmet need to increase the cellular specificity of hyperpolarized 13C MRI measurements of liver tumors. We propose to target hyperpolarized 13C MRI to liver tumors by combining hyperpolarized 13C MRI with a liver- specific gadolinium-based contrast agent that is selectively taken into liver cells. Because the agent is located within liver cells but not tumor cells, it will shorten the T1 (and therefore quench the signal) from hyperpolarized compounds located within liver cells and preserve signal arising from tumor cells (which exclude the gadolinium contrast agent). This exploratory study is intended to test and demonstrate the feasibility of this approach. Using an animal model of metastatic colon cancer, hyperpolarized acquisitions will be performed before and after administration of the gadolinium contrast agent. We will find the dose and timing of contrast injection that maximizes the amount of signal received from liver tumor cells while minimizing the amount of signal received from adjacent normal liver. To our knowledge, this will be the first combination of hyperpolarized 13C imaging with gadolinium contrast agents targeted to a particular cell type. In addition, the suppression of background liver signal is not possible using competing molecular imaging technologies such as FDG-PET, which suggests this technology may create a unique role for hyperpolarized 13C MRI in liver tumor imaging. Finally, if this work is successful, this technology should be rapidly translatable to future studies in humans.