Effect of gallium-porphyrin analogue ATX-70 on nitroxide formation from a cyclic secondary amine by ultrasound: On the mechanism of sonodynamic activation
- National Institutes of Health, Bethesda, MD (United States); and others
Sonodynamic therapy is a promising new modality for cancer treatment based on the synergistic effect on tumor cell killing by combination of a drug (typically a photosensitizer) and ultra-sound. The mechanism of sonodynamic action was suggested to involve photoexcitation of the sensitizer by sonoluminescent light, with subsequent formation of singlet oxygen. In this work we studied the aqueous sonsochemical reactions of the gallium-porphyrin derivative ATX-70, one of the most active sonodynamic agents found, using 50 kHz ultrasound. The experiments were carried out in the presence of 2,2,6,6-tetramethyl-4-piperidone hydrochloride (TMP), which reacts with singlet oxygen or {degrees}OH radicals to give the EPR-detectable nitroxide 2,2,6,6-tetramethyl-piperidone-N-oxyl (TMP-NO). Recently it has been suggested that the enhancement of TMP-NO yields in the presence of aqueous solutions of ATX-70 exposed to ultrasound was evidence for the formation of singlet oxygen in the system. Our results show that the surfactant cetyltrimethylammonium bromide (CTAB) can mimic the ATX-70-induced increase in the TMP-NO signal, but it fails to reproduce the behavior of ATX-70 in D{sub 2}O: while the yields of TMP-NO in the presence of ATX-70 increase in D{sub 2}O, the opposite effect was found with the surfactant CTAB. However, our data show that the increased TMP-NO yields in D{sub 2}O are paralleled by an increased concentration of ATX-70 dimer, a form that is inactive in the photochemical generation of singlet oxygen. Finding the ATX-70-dependent enhancement of the TMP-NO signal was highest at {approximately} 20% O{sub 2}, in both N{sub 2}/O{sub 2} and argon/O{sub 2} mixtures, and decreased with increasing oxygen concentration is not compatible with the singlet oxygen mechanism. Finally, results on the temperature dependence of the ATX-70-induced formation of TMP-NO are not consistent with the photochemical excitation of ATX-70 by sonoluminescent light. 44 refs., 10 figs., 1 tab.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 121757
- Journal Information:
- Radiation Research, Vol. 143, Issue 2; Other Information: PBD: Aug 1995
- Country of Publication:
- United States
- Language:
- English
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