Effect of methotrexate on perfusion and nitrogen-13 glutamate uptake in the Walker-256 carcinosarcoma.
The tissue uptake of [13N]glutamate (glu) was related to that of [11C]butanol (but), a highly diffusible perfusion tracer. In 25 rats bearing Walker-256 carcinomas tumor-to-muscle glu uptake averaged 6.34 +/- 2.84 (s.d.) prior to interventions and the respective uptake of but was 6.79 +/- 3.08 (y = 0.03 + 0.94x). One hour after selective intraarterial administration of methotrexate (mtx), glu uptake fell by 47%, whereas blood flow remained within the pretreatment range (N = 9). Four hours after mtx, perfusion was reduced by approximately 40%, and 2 days later both perfusion and glu uptake reached extremely low levels. No significant difference in the effect of 10 and 50 mg/kg mtx was observed. Regional tissue mtx uptake estimations using 77Br-labeled bromomethotrexate did not reveal any significant uptake in muscle. The relationship between tumor-to-muscle uptake of glu and but (13N/11C-index) was 0.94 +/- 0.015 (s.e.m., N = 25) before intervention. After methotrexate (1 hr, 4 hr, and 2 days) this index was 0.58 +/- 0.06 (N = 9), and 0.85 +/- 0.04 (N = 11) and 1.03 +/- 0.05 (N = 5), respectively. These values demonstrate an early mtx-induced uncoupling of glu uptake with respect to perfusion.
D000818:Animals; D000440:Butanols / Q000493:pharmacokinetics; D002250:Carbon Radioisotopes; D002279:Carcinoma 256, Walker / Q000378:metabolism*; D005971:Glutamates / Q000493:pharmacokinetics*; D018698:Glutamic Acid; D008727:Methotrexate / Q000494:pharmacology*; D009590:Nitrogen Radioisotopes; D051381:Rats; D014018:Tissue Distribution
D000440:Butanols; D002250:Carbon Radioisotopes; D005971:Glutamates; D009590:Nitrogen Radioisotopes; D018698:Glutamic Acid; D008727:Methotrexate