title: The single-pass cerebral extraction and capillary permeability-surface area product of several putative cerebral blood flow imaging agents.
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)3(2MP) 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)(3)2MP 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)(3)2MP and 99mTc-ECD.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, New Brunswick, NJ 08903-0191.
authors.forename: R J
authors.initials: RJ
authors.lastname: Di Rocco
authors.forename: D A
authors.initials: DA
authors.lastname: Silva
authors.forename: B L
authors.initials: BL
authors.lastname: Kuczynski
authors.forename: R K
authors.initials: RK
authors.lastname: Narra
authors.forename: K
authors.initials: K
authors.lastname: Ramalingam
authors.forename: S
authors.initials: S
authors.lastname: Jurisson
authors.forename: A D
authors.initials: AD
authors.lastname: Nunn
authors.forename: W C
authors.initials: WC
authors.lastname: Eckelman
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging*; D002199:Capillary Permeability / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002561:Cerebrovascular Disorders / Q000000981:diagnostic imaging; D007091:Image Processing, Computer-Assisted; D008297:Male; D011849:Radioactive Tracers; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011849:Radioactive Tracers