title: Human pharmacokinetics and radiopharmacological studies of the myocardial perfusion agent: technetium (2-carbomethoxy-2-isocyano-propane)6+.
abstract: The myocardial perfusion agent technetium (2-carbomethoxy-2-isocyano-propane)6+ (99mTc-CPI) is unique from other cationic technetium isonitrile complexes in that it exhibits moderate washout from the heart and rapid hepatobiliary clearance in animal models and human volunteers. Dynamic imaging and HPLC analysis were performed in humans and guinea pigs to outline the pharmacological basis of its pharmacokinetics. Enzymatic hydrolysis of the terminal ester groups in blood was found to occur at a moderate rate producing new species that have been shown not to accumulate in heart tissue. However, after extraction by the heart, liver or kidneys, the 99mTc-CPI complex undergoes metabolism at a much slower rate than observed in the blood. Differences in hydrolysis rate and products obtained indicate separate mechanisms of hydrolysis occurring in blood and other organs. It is proposed that the heart washout occurring after hydrolysis produces a neutral compound which is no longer retained by the negative cytosolic and mitochondrial membrane potentials in myocardial tissue.
authors.affiliation: Department of Radiology, Harvard Medical School, Boston, Massachusetts.
authors.forename: J F
authors.initials: JF
authors.lastname: Kronauge
authors.forename: A S
authors.initials: AS
authors.lastname: Leòn
authors.forename: E S
authors.initials: ES
authors.lastname: Verdera
authors.forename: H S
authors.initials: HS
authors.lastname: Balter
authors.forename: E T
authors.initials: ET
authors.lastname: Leòn
authors.forename: F
authors.initials: F
authors.lastname: Mut
authors.forename: M C
authors.initials: MC
authors.lastname: Oliveira
authors.forename: F A
authors.initials: FA
authors.lastname: Garcia
authors.forename: B L
authors.initials: BL
authors.lastname: Holman
authors.forename: A
authors.initials: A
authors.lastname: Davison
mesh_terms: D000328:Adult; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006168:Guinea Pigs; D006321:Heart / Q000000981:diagnostic imaging*; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D014018:Tissue Distribution
chemical_list: D009570:Nitriles; D015609:Organotechnetium Compounds; C051216:technetium Tc 99m carbomethoxyisopropylisonitrile