Lymphatic Imaging

淋巴管是人体内的第三个循环，是肿瘤扩散的重要途径。淋巴管生成是某些肿瘤的一种特性，使它们能够通过淋巴管增殖。这一过程一直难以研究，因为这些物质很小，难以进入。然而，通过注射各种大分子造影剂，包括放射性标记的、光学标记的和磁性标记的造影剂，可以识别造影剂及其引流模式。此外，在这一过程中获得的知识对原发性和继发性水肿的诊断和管理有影响，这可能是癌症治疗的严重并发症。最后，大分子造影剂的发展对其他疾病也有影响。MIP正在使用成像方法研究肿瘤细胞在癌症中的作用。我们已经发现，直径在5- 10 nm之间的大分子试剂是基于其快速摄取和转运到前哨淋巴结的研究药物的理想选择。前哨淋巴结成像是重要的，因为目前的方法依赖于繁琐的蓝色染料和放射性硫胶体。我们已经开发了一种树枝状聚合物，其被双重标记用于MRI成像和光学成像，这将允许使用MRI和光学成像在没有电离辐射的情况下识别前哨淋巴结。通过比较不同尺寸的树枝状聚合物，实现了淋巴剂的优化。我们发现，非常小的代理人泄漏的反渗透和不满意，而大代理人太慢。因此，负载有钆和光学荧光团的第6代树枝状聚合物是理想的。与其他人合作，我们已经开发和测试了具有新合成的树枝状聚合物，简化了可能的临床转化的化学。然而，我们最终放弃了树枝状聚合物，因为它们从体内清除的时间很长。我们还使用IgG作为淋巴成像的载体分子，并显示其具有生物相容性，大小适合淋巴成像。我们使用两种颜色的QD来研究乳房和手臂到腋窝淋巴结的引流，发现一些小鼠具有独立的引流系统，而其他小鼠表现出双重引流淋巴结，即部分引流乳房和部分引流肢体的淋巴结。此外，我们还探索了同时使用多达5个不同波长的QD，以建立头部和颈部的复杂淋巴引流模式。然而，量子点的生物相容性令人担忧。我们与波士顿儿童医院合作开发了一种用于原发性脑水肿儿童的MR造影剂。我们发现，钆注射到猪的脚迅速浑浊的胸导管。然而，更好的技术已经出现，其中钆注射到腹股沟淋巴结。Ferumoxytol是一种含铁的氧化物，在正常的节点中积累。我们正在GU恶性肿瘤患者中测试这种药物，以确定静脉给药是否适用于检测淋巴结转移。一项针对20名前列腺癌患者的初步研究已经结束，今年发表了一项新的研究。我们与HIV/AIDS小组合作，了解结肠的淋巴引流。我们正在开发一种通过识别与炎症区域相关的“前哨”淋巴结来识别相关淋巴结的方法。通过了解影像学上的引流模式，可以更好地了解HIV诱导的结肠炎的机制。此外，我们正在研究慢性感染SIV的动物的结构成像变化，显示纤维化。

The lymphatics represent the third circulation in the body and are an important route of spread for tumors. Lymphangiogenesis is a property of some tumors that allows them to propagate via the lymphatics. This process has been difficult to study because the lymphatics are small and inaccessible. However, by injecting various kinds of macromolecular contrast agents, including radiolabeled, optically labeled and magnetically labeled it is possible to identify the lymphatics and their drainage patterns. Moreover, the knowledge gained in this process has implications for the diagnosis and management of primary and secondary lymphedema, which can be a serious complication of cancer therapy. Finally, the development of macromolecular contrast agents has implications for other diseases. The MIP is investigating the role of the lymphatics in cancer using imaging methods. We have found that macromolecular agents of between 5-10nm in diameter are ideal for studying the lymphatics based on their rapid uptake and transit to the sentinel nodes. Sentinel node imaging is of importance because current methods rely on cumbersome blue dyes and radioactive sulfur colloid. We have developed a dendrimer that is dual labeled for MRI imaging and optical imaging that would allow the identification of the sentinel node without ionizing radiation using MRI and optical imaging. By comparing different sized dendrimers optimization of the lymphatic agent was achieved. We found that very small agents leaked from the lymphatics and were unsatisfactory whereas large agents were too slow. Therefore, the Generation 6 dendrimer loaded with Gadolinium and an optical fluorophore was ideal ideal. Working others, we have developed and tested dendrimers with new syntheses that simplified the chemistry for possible clinical translation. However, we ultimately abandoned dendrimers because of their very long clearance times from the body. We have also used IgG as a carrier molecule for lymphatic imaging and shown it to be a biocompatible and suitably sized for lymphatic imaging. We have employed two color QDs to investigate the drainage of the breast and arm to the axillary lymph nodes and found that some mice had independent drainage systems whereas other mice demonstrated dual draining nodes , i.e. nodes that partly drained the breast and partly drained the limb. Additionally we have explored the use of up to 5 QDs of differing wavelength simultaneously in order to establish the complex lymphatic drainage patterns in the head and neck. However, the biocompatibility of QDs is a concern. We collaborated with Boston Childrens Hospital to develop a MR contrast agent for use in children with primary lymphedema. We found that gadolinium injected into the foot of pigs quickly opacified the thoracic duct. However, better techniques have emerged in which gadolinium is injected into inguinal lymph nodes. Ferumoxytol is an iron containing oxide that accumulates in normal nodes. We are testing this agent in patients with GU malignancies to see if intravenous administration is suitable for detecting lymph node metastases. A preliminary study of 20 patients with prostate cancer has concluded and a new study was published this year. We collaborated with the HIV/AIDS group to understand the lymphatic drainage of the colon. We are developing a method of identifying the relevant lymph nodes by identifying the "sentinel" nodes related to areas of inflammation. In understanding the drainage patterns on imaging it may be possible to better understand the mechanisms of HIV induced colitis. Additionally we are studying structural imaging changes in chronically infected animals with SIV demonstrating fibrosis.