title: [Preclinical pharmacological study of a novel myocardial perfusion agent: 99mTc-Q3].
abstract: In order to provide an experimental foundation for clinical study, we made a preclinical pharmacological investigation of 99mTc-Q3, a novel myocardial perfusion imaging agent, technetium-99m-N,N'-ethylenebis (acetylace-toneiminato) bis (tris (3-methoxy-1-proply) phosphine). After the preparation of this compound, the kinetics of blood clearance in rabbits, biodistribution in mice, measurement of plasma protein binding rate, and myocardial perfusion imaging in dog were carried out. The labelling efficiency and radiochemical purity measured were over 99%, and the stability (in vitro) was good and stable up to 6 hr of testing at room temperature. The pharmacokinetics met the two-compartment model with 0.23 +/- 0.09 ml/min of excellent blood clearance, an initial half-time of 1.5979 +/- 0.4182 min, and a late half-time of 203 +/- 25.83 min. The biodistribution as shown in myocardial accumulation was earlier, the radioactive value was higher, and once extracted, it remained relatively constant in the myocardium for at least 4 hr. The tracer was rapidly cleared from the blood, lung and the liver. The scintigraphy imaging in dog demonstrated that it was rapidly cleared from the lung, and the radioactive concentration approached that of background 1 hr after injection. At 15 min after injection, the myocardial imaging displayed clearly up to 3 hr. In vitro protein binding rate was low (7.13 +/- 0.42%). The tolerance of this drug in mice was 500 times as much as in humans. In conclusion, 99mTc-Q3 exhibits favorable stability, biological property and safety, so clinical study of this preparation as a myocardial perfusion imaging agent is worthwhile.
authors.affiliation: Department of Nuclear Medicine, First Affiliated Hospital, WCUMS, Chengdu 610041.
authors.forename: C
authors.initials: C
authors.lastname: Fan
authors.forename: T
authors.initials: T
authors.lastname: Tan
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: A
authors.initials: A
authors.lastname: Kuang
authors.forename: Z
authors.initials: Z
authors.lastname: Liang
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D006321:Heart / Q000000981:diagnostic imaging*; D008657:Metabolic Clearance Rate; D051379:Mice; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D010720:Phosphines / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits; D011877:Radionuclide Imaging; D014018:Tissue Distribution
chemical_list: D015609:Organotechnetium Compounds; D010720:Phosphines; C081212:technetium Tc 99m Q3