A total of 72 RG-2 transplanted
gliomas were studied in 58 rats at three time points (1, 30, 240 min) after
intravenous injection of [125I]
radioiodinated serum albumin ([125I]RISA). The animals were divided into two groups: a control group that received no treatment and a second group that was treated with five doses of 1.5 mg/kg of
dexamethasone over 2.5 days. Local tissue concentrations of [125I]RISA were measured with quantitative autoradiography based on morphological features of the
tumors and used to calculate the tissue distribution space. Two models were used to analyze the data. A two compartment model yielded estimates of local blood-to-tissue influx constants (K1), lower limit extracellular volumes (Ve), and plasma vascular volumes (Vp) in different
tumor regions. Treatment with
dexamethasone consistently reduced the RISA distribution space in the RG-2
tumors; the reduction in Ve was statistically significant in almost all
tumor regions: whole
tumor Ve (mean +/- SE) was reduced from 0.14 +/- 0.02 ml g-1 in control animals to 0.08 +/- 0.01 ml g-1 in
dexamethasone treated animals. K1 and Vp were also decreased in all
tumor regions
after treatment with
dexamethasone (whole
tumor K1 decreased from 2.36 +/- 0.89 to 0.83 +/- 0.29 microliter g-1 min-1 and Vp decreased slightly from 0.016 +/- 0.013 to 0.010 +/- 0.005 ml g-1 after
dexamethasone treatment), but these changes were not statistically significant. A comparison of the
tumor influx constants in control animals and the aqueous diffusion constants of two different size molecules (RISA and aminoisobutyric
acid) suggests that the "pores" across RG-2 capillaries are large and may not restrict the free diffusion of RISA (estimated minimum pore diameter greater than 36 nm) and that the total pore area is approximately 6.2 X 10(-5) cm2 g-1 in RG-2
tumor tissue. The second model, which allows for diffusion and
solvent drag of RISA across
tumor capillaries and through the tissue, was used to analyze the distribution profiles of RISA in peripheral
tumor and adjacent brain. This analysis was consistent with a small bulk flow of plasma-derived
edema fluid (capillary filtration rate approximately equal to 0.8 microliter g-1 min-1) and a larger component of free diffusion of RISA (K approximately equal to 2 microliter g-1 min-1) through pores in the
tumor vessels of control animals.
Dexamethasone treatment markedly reduced or eliminated the filtration of plasma-derived fluid across
tumor capillaries and the movement of RISA through the extracellular space by
solvent drag.(ABSTRACT TRUNCATED AT 400 WORDS)