Breast Tumor pH: Design Evaluation and Application of Novel Reporter Molecules
Final rept. 1 Oct 1999-30 Sep 2003
TEXAS UNIV SOUTHWESTERN MEDICAL SCHOOL AT DALLAS
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Systematic drugs are one of the most potent means for controlling breast cancer. Their ability to kill cancer cells often depends, however, on the presence of appropriate physiological conditions. For instance, exciting recent results suggest that uptake and retention of 5-fluorouracil 5-FU in tumors may be influenced by pH, in particular, the trans membrane pH gradient. We designed novel19F NMR reporter molecules to investigate breast tumor pH. Several syntheses of novel molecules have been successful e.g., trifluoromethyl pyridoxol and he molecules have been characterized in vitro and evaluated in vivo. Certain strategic molecular goals proved to be intractable, but have provided valuable lessons in synthetic chemistry. The new indicators have provided non-invasive measurements of extra cellular pH in breast tumors, which is an important step towards understanding factors modulating chemotherapy. This research also laid a foundation for a novel concept in gene therapy, 19F NMR reporter molecules based on the fluoronitrophenol galactoside structure.
- Medicine and Medical Research