title: Hexakis(carbomethoxyisopropylisonitrile) technetium(I), a new myocardial perfusion imaging agent: binding characteristics in cultured chick heart cells.
abstract: Cellular kinetics and binding characteristics of hexakis(carbomethoxyisopropylisonitrile) technetium(I) (Tc-CPI), a new cationic, highly lipophilic myocardial perfusion imaging agent, were evaluated in chick embryo heart cells grown in monolayer culture. Myocytes showed uptake of Tc-CPI to a plateau level with a half-time (t1/2) of 4.1 +/- 0.7 min (mean +/- s.e.m.; n = 6); t1/2 appeared independent of extracellular Tc-CPI concentration. Plateau level Tc-CPI uptakes (10(-16) to 10(-11) mole Tc-CPI/mg cell protein) were a linear function of extracellular Tc-CPI concentration (range: 10(-13)M to 10(-8)M, respectively). Tracer 99mTc-CPI uptake (binding) was not competitively displaced by carrier 99Tc-CPI. Uptake was temperature-sensitive; however, several inhibitors of cationic membrane transport (ouabain, amiloride, bumetanide, and verapamil) showed no significant effect. Extreme alkalinization of external load solution (pHo approximately 8.5) partially inhibited Tc-CPI uptake; however, intracellular pH changes showed no effect. Washout from contractile preparations could be described by a two component system: a fast component (myocytes) with a t1/2 approximately 4.5 min and a slow component (fibroblasts) with a t1/2 approximately 40 min. Cell fractionation experiments showed most of the activity to be associated with the cell membrane fraction. The data do not demonstrate a specific mechanism for uptake of Tc-CPI; however, results suggest binding to myocytes in a manner proportional to the delivery of the complex to the extracellular spaces. Such properties would be desirable for a myocardial perfusion imaging agent.
authors.affiliation: Dept. of Radiology, Brigham and Women's Hospital, Boston, MA 02115.
authors.forename: D
authors.initials: D
authors.lastname: Piwnica-Worms
authors.forename: J F
authors.initials: JF
authors.lastname: Kronauge
authors.forename: B L
authors.initials: BL
authors.lastname: Holman
authors.forename: J
authors.initials: J
authors.lastname: Lister-James
authors.forename: A
authors.initials: A
authors.lastname: Davison
authors.forename: A G
authors.initials: AG
authors.lastname: Jones
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D006321:Heart / Q000000981:diagnostic imaging*; D009200:Myocardial Contraction; D009570:Nitriles; D009942:Organometallic Compounds; D015609:Organotechnetium Compounds; D011877:Radionuclide Imaging; D013667:Technetium; D014018:Tissue Distribution
chemical_list: D009570:Nitriles; D009942:Organometallic Compounds; D015609:Organotechnetium Compounds; C051216:technetium Tc 99m carbomethoxyisopropylisonitrile; D013667:Technetium