EFFECT OF GALLIUM-PORPHYRIN ANALOG ATX-70 ON NITROXIDE FORMATION FROMA CYCLIC SECONDARY AMINE BY ULTRASOUND - ON THE MECHANISM OF SONODYNAMIC ACTIVATION

Sonodynamic therapy is a promising new modality for cancer treatment b ased on the synergistic effect on tumor cell killing by combination of a drug (typically a photosensitizer) and ultrasound, The mechanism of sonodynamic action was suggested to involve photoexcitation of the se nsitizer by sonoluminescent light, with subsequent formation of single t oxygen. In this work we studied the aqueous sonochemical reactions o f the gallium-porphyrin derivative ATX-70, one of the most active sono dynamic agents found, using 50 kHz ultrasound. The experiments were ca rried out in the presence of 2,2,6,6-tetramethyl-4-piperidone hydrochl oride (TMP), which reacts with singlet oxygen or (OH)-O-. radicals to give the EPR-detectable nitroxide 2,2,6,6-tetramethyl-4-piperidone-N-o xyl (TMP-NO), Recently it has been suggested that the enhancement of T MP-NO yields in the presence of aqueous solutions of ATX-70 exposed to ultrasound was evidence for the formation of singlet oxygen in the sy stem. Our results show that the surfactant cetyltrimethylammonium brom ide (CTAB) can mimic the ATX-70-induced increase in the TMP-NO signal, but it fails to reproduce the behavior of ATX-70 in D2O: while the yi elds of TMP-NO in the presence of ATX-70 increase in D2O, the opposite effect was found with the surfactant CTAB, However, our data show tha t the increased TMP-NO yields in D2O are paralleled by an increased co ncentration of ATX-70 dimer, a form that is inactive in the photochemi cal generation of singlet oxygen. Our finding that the ATX-70-dependen t enhancement of the TMP-NO signal was highest at similar to 20% O-2, in both N-2/O-2 and argon/O-2 mixtures, and decreased with increasing oxygen concentration is not compatible with the singlet oxygen mechani sm, Finally, our results on the temperature dependence of the ATX-70-i nduced formation of TMP-NO are not consistent with the photochemical e xcitation of ATX-70 by sonoluminescent light: the ATX-70-dependent enh ancement of TMP-NO signal increased with temperature in the range 10-2 5 degrees C, while the intensity of sonoluminescence of aqueous soluti ons both in multiple-bubble fields and in single-bubble experiments is known to decrease with increasing temperature. (C) 1995 by Radiation Research Society