Effects of texaphyrins on the oxygenation of EMT6 mouse mammary tumors

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 pO(2) histograph when tumors, implanted intradermally in the rear dorsum, reached 150-200 mm(3). 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 pO(2) 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 mumol/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. (C) 2004 Elsevier Inc.