Growth Factor Imaging

血管生成受几种生长因子的调控，这些生长因子导致高通透性血管的形成。血管生成血管的这种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感兴趣的话题。我们已经开发了基于不同分子量的树状分子来测量肿瘤的渗透性和肾脏排泄。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，并不是所有的病人都能从这种疗法中受益。我们与Martin Brechbiel博士合作开发了一种111In标记的赫赛汀扫描，可以可视化HER2/neu受体在体内和肿瘤内的分布。这种药物已经在老鼠身上进行了彻底的评估，已经在0期研究中获得了引入人体的初步批准。我们正在与DDG合作生产这种药物，用于临床中心的人体试验，以评估赫赛汀的生物分布和监测反应。这项研究将为未来使用与赫赛汀螯合的α -发射器放射免疫治疗的试验估计剂量奠定基础，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.