Growth Factor Imaging

血管生成由几种生长因子调节，导致高渗透性血管。血管生成血管的这一特性可以在临床和动物研究中利用动态增强MRI成像。大分子造影剂可能能够更准确地测量血管生成，因此是MIP感兴趣的主题。我们已经开发了不同分子量的基于树枝状聚合物的分子来测量肿瘤渗透性和肾排泄。其他生长因子也可以成像。赫赛汀是一种成功的临床药物，无论是单药治疗还是联合治疗，都能对抗乳腺癌。然而，并非所有患者都能从这种治疗中获益。我们与Martin Brechbiel博士合作开发了一种111 In标记的赫赛汀扫描仪，可以可视化体内和肿瘤内HER 2/neu受体的分布。该药物已在小鼠中进行了全面评估，已初步批准在0期研究中引入人体。我们与DDG合作，正在临床中心生产这种用于人体试验的药物，以评估赫赛汀的生物分布并监测反应。这项研究将作为未来试验的剂量学评估基础，这些试验使用与赫赛汀螯合的α-发射体进行放射免疫治疗，特别是在腹膜转移性疾病中。

Angiogenesis is regulated by several growth factors that lead to highly permeable blood vessels. This property of angiogenic vessels can be exploited with dynamic enhanced MRI imaging in the clinic and in animal studies. Macromolecular contrast agents may be able to measure angiogenesis more accurately and thus are a topic of interest to the MIP. We have developed dendrimer based molecules of varying molecular weight to measure tumor permeability and renal excretion. Other growth factors can also be imaged. Herceptin is a successful clinical agent, both in monotherapy and in combination therapy, in the fight against breast cancer. However, not all patients will benefit from this therapy. In conjunction with Dr. Martin Brechbiel we have developed a 111In labeled Herceptin Scan that enables the visualization of the distribution of HER2/neu receptors in the body and within tumors. This agent, which has been thoroughly evaluated in mice, has received preliminary approval for introduction into man in a Phase 0 study. In collaboration with the DDG we are manufacturing this agent for use in human trials in the Clinical Center to assess the biodistribution of Herceptin and monitor response. This study will serve as a basis for estimating dosimetry for future trials using radioimmunotherapy with alpha-emitters chelated to Herceptin, particularly in metastatic disease localized to the peritoneum.