Effect of methotrexate on perfusion and nitrogen-13 glutamate uptake in the Walker-256 carcinosarcoma
The tissue uptake of (/sup 13/N)glutamate (glu) was related to that of (/sup 11/C)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 /sup 77/Br-labeled bromomethotrexate did not reveal any significant uptake in muscle. The relationship between tumor-to-muscle uptake of glu and but (/sup 13/N//sup 11/C-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.
- Research Organization:
- Institute of Nuclear Medicine, Heidelberg (Germany F.R.)
- OSTI ID:
- 5169408
- Journal Information:
- J. Nucl. Med.; (United States), Vol. 29:2
- Country of Publication:
- United States
- Language:
- English
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CARBON 11
ISOTOPE RATIO
GLUTAMIC ACID
UPTAKE
METHOTREXATE
BIOLOGICAL EFFECTS
NITROGEN 13
BROMINE 77
CARCINOMAS
PERFUSED TISSUES
RATS
TISSUE DISTRIBUTION
TRACER TECHNIQUES
AMINO ACIDS
ANIMAL TISSUES
ANIMALS
ANTIMETABOLITES
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BODY
BROMINE ISOTOPES
CARBON ISOTOPES
CARBOXYLIC ACIDS
DAYS LIVING RADIOISOTOPES
DISEASES
DISTRIBUTION
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
EVEN-ODD NUCLEI
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MINUTES LIVING RADIOISOTOPES
NEOPLASMS
NITROGEN ISOTOPES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
RADIOISOTOPES
RODENTS
TISSUES
VERTEBRATES
550901* - Pathology- Tracer Techniques