Metabolic and kinetic considerations in the use of [125I]HIPDM for quantitative measurement of regional cerebral blood flow.

The metabolic degradation and the kinetics of the cerebral uptake of N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-[125I]iodobenzyl)-1, 3-propanediamine ([125I]HIPDM) have been studied in conscious, adult male Sprague-Dawley rats to determine its suitability as a tracer for the quantitative measurement of regional CBF (rCBF). rCBF was calculated by the indicator fractionation and the tissue equilibration methods in experiments of different durations up to 1 h. The values of rCBF obtained with [125I]HIPDM were compared with those obtained in concurrent measurements with [14C]iodoantipyrine in the same animals. Results of the experiments demonstrate that [125I]HIPDM is an inadequate tracer for use with the indicator fractionation method and that any method that employs [125I]HIPDM for the determination of rCBF must take into account its metabolic degradation, diffusion limitations, and bidirectional flux across the blood-brain barrier. With the tissue equilibration method, consistent determinations of rCBF may be possible with [125I]HIPDM by measurement of the time course of its concentration in arterial blood, corrected for the presence of 125I-labeled metabolic products, and its concentration in the brain at any time up to 1 h after its administration. The method may be adapted to measure rCBF in humans by means of single-photon emission tomography with [123I]HIPDM.