Determination of flow and rate constants in a kinetic model of [99mTc]-hexamethyl-propylene amine oxime in the human brain.

The values for flow and rate constants for a kinetic model of [99mTc]-hexamethylpropyleneamine oxime (HM-PAO) distribution in the human brain were determined. The single-pass extraction ratio of HM-PAO was also determined in the rat brain by the indicator diffusion method; a value of 0.90 +/- 0.02 (mean +/- SEM, n = 5) was obtained. Time course data of brain activity and arterial blood activity of the tracer were fitted to a four compartment model: Values of blood flow and the first-order rate constants for backdiffusion of the diffusible tracer from brain to blood (k2), conversion of the lipophilic tracer to the hydrophilic one in brain (k3), and conversion of the diffusible tracer to the nondiffusible one in blood (k5) were determined. Conversion of hydrophilic tracer back to a lipophilic form in both blood and brain was assumed to be negligible during the course of the experiment. The values obtained for blood flow, k2, and k3 were, respectively, 0.40 +/- 0.03 ml/g/min, 0.38 +/- 0.04 min-1, and 0.92 +/- 0.05 min-1 in the gray matter (n = 4), and 0.23 +/- 0.01 ml/g/min, 0.17 +/- 0.01 min-1, and 1.01 +/- 0.05 min-1 in the white matter (n = 2) in patients with cerebrovascular disorder. The k5 value was 1.14 +/- 0.06 min-1 (n = 4). These experimentally determined values agree well with the theoretical ones previously reported by Lassen et al. The results suggest the relative constancy of the k3 and k5 values and the more prominent initial backdiffusion of the lipophilic HM-PAO from brain to blood in high flow regions compared to low flow regions.