Effect of Methotrexate on Perfusion and Nitrogen-13 Glutamate Uptake in the Walker-256 Carcinosarcoma

• Published in: The Journal of nuclear medicine (1978) Vol. 29; no. 2; pp. 208 - 216
• Main Authors: Knapp, Wolfram H, Panzer, Monika, Helus, Frantisek, Layer, Klaus, Sinn, Hans-Jorg, Ostertag, Hermann
• Format: Journal Article
• Language: English
• Published: United States Soc Nuclear Med 01.02.1988
• Subjects: Animals; Butanols - pharmacokinetics; Carbon Radioisotopes; Carcinoma 256, Walker - metabolism; Glutamates - pharmacokinetics; Glutamic Acid; Methotrexate - pharmacology; Nitrogen Radioisotopes; Rats; Tissue Distribution
• ISSN: 0161-5505; 1535-5667

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.