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Blood–Cerebrospinal Fluid and Blood‐Brain Barriers Imaged by 18 F‐Labeled Metabolites of 18 F‐Setoperone Studied in Humans Using Positron Emission Tomography
Author(s) -
Blin Jérôme,
Crouzel Christian
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb10978.x
Subject(s) - choroid plexus , metabolite , free fraction , radioligand , metabolism , chemistry , kinetics , cerebrospinal fluid , positron emission tomography , blood–brain barrier , receptor , nuclear medicine , central nervous system , endocrinology , biochemistry , medicine , biology , plasma protein binding , physics , quantum mechanics
18 F‐Setoperone, a sensitive radioligand for brain serotonin 5‐HT 2 receptor positron emission tomography studies, is metabolized into 18 F‐labeled metabolites, which participate in blood 18 F radioactivity. Its main metabolite, identified as reduced 18 F‐setoperone, was synthesized and studied in humans to determine if 18 F‐labeled metabolites of 18 F‐setoperone (a) enter into the brain, (b) bind to the 5‐HT 2 receptor, and (c) explain the increase of 18 F radioactivity in the free fraction in blood measured following 18 F‐setoper‐one injection. After reduced 18 F‐setoperone injection, the brain‐to‐blood 18 F radioactivity concentration ratio (a) was low, at the beginning, indicating that this metabolite did not cross the blood‐brain barrier; (b) was increased thereafter, with a higher radioactivity level in the choroid plexus than in brain tissue, suggesting a blood‐CSF barrier crossing due to radioligand hydrophilicity; and (c) showed similar kinetics for cerebellum and frontal cortex, indicating that radioactive metabolites of 18 F‐setoperone did not bind to the 5‐HT 2 receptor. Because hydrophilic 18 F‐labeled metabolites of 18 F‐setoperone increased 18 F radioactivity in the free fraction in blood, we quantified the relation between 18 F‐se‐toperone metabolism and free fraction kinetics in blood. A significant negative correlation was found between metabolism and free fraction rate constants in blood, showing it was possible to predict the 18 F‐setoperone metabolism rate using free fraction kinetics in blood. This will allow us to avoid the use of radio‐TLC, a reference method that is difficult to use when multiple samples must be analyzed. A hydrophilic positron‐emitter radioligand could also be used to study the blood‐CSF barrier.