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The Single-Pass Cerebral Extraction and Capillary Permeability-Surface Area Product of Several Putative Cerebral Blood Flow Imaging Agents

The Bristol-Myers Squibb Pharmaceutical Research Institute, New Brunswick, New Jersey

Correspondence: For correspondence or reprints contact: Richard J. Di Rocco, The Bristol-Myers Squibb Pharmaceutical Research Group, 1 Squibb Dr., P.O. Box 191, New Brunswick, NJ 08903-0191.

ABSTRACT

We have determined cerebral blood flow (CBF) and the single-pass cerebral extraction (E) of several putative agents for external imaging of CBF. Simultaneous measurements of blood flow and extraction were performed in 106 rats. For all agents, comparison of linear and exponential regressions of E on CBF indicates that this relationship can be described as linear over the range of flows studied. Analysis of covariance indicates that the extraction of ¹²³I-IMP, ⁶⁷Cu-PTSM and ^99mTc-HMPAO is higher than that of ^99mTc-Cl(DMG) ₃2MP and ^99mTc-ECD, particularly at flows above the normal range. Accordingly, for ¹²³I-IMP, ⁶⁷Cu-PTSM and ^99mTc-HMPAO, the slope of the linear regression equation for the relationship between brain capillary permeability surface area product (PS) and CBF is higher than that for ^99mTc-Cl(DMG) ₃2MP and ^99mTc-ECD. PS varies as a linear function of CBF over the range of flows studied. At a CBF level that corresponds to normal regional CBF for human cortex, 0.5 ml/g/min, all the agents have a single-pass extraction of approximately 70% or greater. While all the agents detected changes in CBF in the normal to ischemic range, at higher flows ¹²³I-IMP, ⁶⁷Cu-PTSM and ^99mTc-HMPAO showed substantially greater fidelity to true CBF than ^99mTc-Cl(DMG) ₃2MP and ^99mTc-ECD.

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