Effects of texaphyrins on the oxygenation of EMT6 mouse mammary tumors.

ABSTRACT

PURPOSE: To investigate the effects of texaphyrins on the oxygenation of EMT6 mouse mammary tumors in Balb/c Rw mice. Texaphyrins are synthetic, porphyrin-like molecules capable of stably coordinating lanthanide and nonlanthanide metals. Metallotexaphyrin compounds containing gadolinium (MGd), lutetium (MLu), europium (Eu-Tex), dysprosium (Dy-Tex), and manganese (Mn-Tex) were evaluated. METHODS: Tumor oxygenation was measured using an Eppendorf pO2 histograph when tumors, implanted intradermally in the rear dorsum, reached 150-200 mm3. Oxygen measurements were also made in the leg muscle of tumor-bearing mice, to determine whether changes in oxygenation occurred in nontumor tissue. RESULTS: Motexafin gadolinium (Xcytrin, MGd) seems to be an effective modulator of tumor oxygen tension. The mean of the median tumor pO2 6 hours after injection of MGd was 8.0 +/- 2.4 mm Hg. The control value was 1.5 +/- 0.4 mm Hg. The oxygen levels within EMT6 tumors were shifted significantly toward higher oxygen tensions 6-8 hours after i.v. injection of 40 micromol/kg MGd, thereby reducing the percentage of severely hypoxic readings (MGd, 6 hours 44.6 +/- 4.3% <2.5 mm Hg; CONTROL 69.4 +/- 3.0% <2.5 mm Hg). There was no significant change in the oxygenation of the leg muscle after MGd treatment. Eu-Tex and Mn-Tex increased the tumor oxygenation to a much lesser degree than MGd. MLu, Dy-Tex, and the vehicle (a 5% mannitol solution) did not modulate tumor oxygenation. CONCLUSIONS: MGd is an effective modulator of tumor oxygenation. The central metal composition of texaphyrin compounds is an important determinant of the effect of the texaphyrins on tumor oxygenation.