Permeability limitation in estimation of local brain blood flow with [14C]antipyrine

Influence of capillary permeability on local cerebral blood flow (LCBF) estimated by the autoradiograhpic diffusible-indicator method was analyzed by computer simulation. Its influence increases with increasing flow. With normal perfusion rates in gray matter, capillary permeability coefficient x surface area (PS value) must exceed 0.12 cm3-s(-1)-g(-1) for estimated LCBF to attain 95% of true values in all structures. In white matter, with its lower perfusion rates, the PS value must exceed 0.035 cm3-s(-1)-g(-1) for equivalent accuracy. [14C]antipyrine, widely used in the LCBF technique, has a PS value below these values and leads to undersestimation of LCBF. Experimental studies in cats in which LCBF was measured with either [14C]antipyrine or the freely diffusible, radioactive gas, [131I]trifluoroiodomethane, demonstrated consistently lower estimates of LCBF with [14C]antipyrine than with the gas; the deviations in the various cerebral structures approximated those predicted by the theoretical analyses. These results suggest that the uptake of [14C]antipyrine by cerebral tissues is diffusion limited as well as flow limited, and it therefore is not an ideal tracer for the autoradiographic LCBF technique.