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The Journal of Nuclear Medicine Vol. 29 No. 2 208-216
© 1988 by Society of Nuclear Medicine
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Effect of Methotrexate on Perfusion and Nitrogen-13 Glutamate Uptake in the Walker-256 Carcinosarcoma

Wolfram H. Knapp, Monika Panzer, Frantisek Helus, Klaus Layer, Hans-Jörg Sinn and Hermann Ostertag

Institute of Nuclear Medicine, German Cancer Research Center, Heidelberg, FRG

Correspondence: For reprints contact Prof.Dr.med. W.H. Knapp, Institute of Nuclear Medicine, Herzzentrum Nordrhein-Westfalen, 4970 Bad Oeynhausen, FRG.

ABSTRACT

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 pre-treatment range (N = 9). Four hours after mtx, perfusion was reduced by ~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.

FOOTNOTES

Dedicated to Professor Dr. Ludwig E. Feinendegen on the occasion of his 60th birthday.






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Copyright © 1988 by the Society of Nuclear Medicine.