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


METHODS
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.
Donnelly
Erling T
ET
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520-8040, USA.
Liu
Yanfeng
Y
Fatunmbi
Yetunde O
YO
Lee
Intae
I
Magda
Darren
D
Rockwell
Sara
S
D000818:Animals; D015687:Cell Hypoxia; D019069:Cell Respiration / Q000187:drug effects*; D004419:Dysprosium / Q000494:pharmacology; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D017895:Manganese Compounds / Q000494:pharmacology; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010100:Oxygen / Q000378:metabolism*; D011166:Porphyrins / Q000494:pharmacology*
D017895:Manganese Compounds; D008665:Metalloporphyrins; D011166:Porphyrins; C442892:texaphyrin; C102825:motexafin lutetium; D004419:Dysprosium; C437683:motexafin gadolinium; D010100:Oxygen