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.
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