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.
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Authors | Erling T Donnelly, Yanfeng Liu, Yetunde O Fatunmbi, Intae Lee, Darren Magda, Sara Rockwell |
Journal | International journal of radiation oncology, biology, physics
(Int J Radiat Oncol Biol Phys)
Vol. 58
Issue 5
Pg. 1570-6
(Apr 01 2004)
ISSN: 0360-3016 [Print] United States |
PMID | 15050338
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Manganese Compounds
- Metalloporphyrins
- Porphyrins
- texaphyrin
- motexafin lutetium
- Dysprosium
- motexafin gadolinium
- Oxygen
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Topics |
- Animals
- Cell Hypoxia
- Cell Respiration
(drug effects)
- Dysprosium
(pharmacology)
- Mammary Neoplasms, Animal
(metabolism)
- Manganese Compounds
(pharmacology)
- Metalloporphyrins
(pharmacology)
- Mice
- Mice, Inbred BALB C
- Oxygen
(metabolism)
- Porphyrins
(pharmacology)
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