Pharmacodynamics of Gemcitabine by MRS in Pancreatic CA

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DESCRIPTION (provided by applicant): Some 30,000 Americans contracted pancreatic cancer last year, and, 29,900 (99.7%) of them succumbed to their disease. Pancreatic cancer accounts for approximately 25% of all Gl neoplasms, and is by far the one with the worst prognosis. Indeed, with a mean life expectancy from diagnosis of only 3 months, this disease represents one of the grimmest fronts of the War on Cancer. Currently there is only one FDA approved drug for the treatment of this disease, Gemcitabine, a nucleoside antimetabolite. Unfortunately, multiple phase III trials using single agent Gemcitabine at the FDA approved dose and schedule have shown, (i) a consistent response rate of only <10%; (ii) median survival of approximately 6 months; and (iii) one year survival rates of <20%. Recent phase II data, however, have suggested that the rate of delivery of gemcitabine can have a favorable impact on the median survival. Consequently, our overarching hypothesis is that the amount and rate of Gemcytabine uptake and anababolism in the tumor will correlate with that particular individual patient response. Validating this assumption is crucial in order to be able to customize dose and administration rate and regimens to each individual patient. To test this hypothesis we propose to apply localized Fluorine Magnetic Resonance Spectroscopy (19F-MRS) at ultra high magnetic field of 7 Tesla, for non invasive, in vivo monitoring the drug and its active anabolic by product di-fluoro, de-oxycytadine tri-phosphate (dFdCTP).