Our first generation pH indicator (6-fluoropyridoxol) has been successfully observed in vivo to detect the transmembrane pH gradient which was found to be reversed compared with normal tissue. A new analog 6-fluoropyridoxamine has been prepared with a pKa of 7.05 and its utility has been demonstrated in whole blood and the perfused heart. pH is thought to strongly influence the uptake and retention of various chemotherapeutic drugs and we have initiated studies of the pharamcokinetics of 5-fluorouracil and the pro-drug 5-fluorocytosine. pH and drug clearance may be observed simultaneously in tumors in vivo. (Service 8) REPORT PERIOD: (09/01/97-08/31/98)
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