title: Effects of extracellular Na+ and Ca2+ ions and Ca2+ channel modulators on the cell-associated activity of 99mTc-MIBI and 99mTc-tetrofosmin in tumour cells.
abstract: Our aim was to determine whether the Ca2+ ion or cell membrane Ca2+ and Na+/Ca2+ ion transport systems are involved in maintaining the cell-associated activity of technetium-99m-hexakis-methoxy-isobutyl-isonitrile (99mTc-MIBI) and technetium-99m-ethylene-bis[bis(2-ethoxyethyl)phosphin] (99mTc-tetrofosmin) in tumour cell lines. The cell-associated activities of 99mTc-MIBI and 99mTc-tetrofosmin were assessed in various buffers, with or without Na+ and/or with different concentrations of Ca2+, in Lewi's murine lung cell carcinoma and human glioma cell lines. Different Ca2+ channel modulators, such as verapamil, flunarizine and 3,4-dichlorobenzamil (DCB), were used to assess the effect of Ca2+ channels on the cell-associated activity of 99mTc-MIBI and 99mTc-tetrofosmin. Despite significant differences between cell lines, the cell-associated activity of 99mTc-MIBI was higher in buffers without extracellular Ca2+ and Na+. The cell-associated activity of 99mTc-MIBI was significantly lower in all buffers containing high concentrations of Ca2+ in both cell lines. The cell-associated activity of Tc-tetrofosmin was also significantly higher in buffers without Ca2+, and was significantly decreased in buffers with high concentrations of Ca2+. All modulators significantly increased the cell-associated activity of 99mTc-MIBI in both cell lines in all buffers. All modulators increased the cell-associated activity of 99mTc-tetrofosmin, particularly in buffers containing Ca2+. The cell-associated activities of both 99mTc-MIBI and 99mTc-tetrofosmin may be dependent on verapamil-, flunarizine- and DCB-sensitive Ca2+ channels.
authors.affiliation: Department of Radiology, Yamanashi Medical University, Yamanashi, Japan. saali@cc.nih.gov
authors.forename: A S
authors.initials: AS
authors.lastname: Arbab
authors.forename: J
authors.initials: J
authors.lastname: Ueki
authors.forename: K
authors.initials: K
authors.lastname: Koizumi
authors.forename: T
authors.initials: T
authors.lastname: Araki
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D005444:Flunarizine / Q000494:pharmacology; D005910:Glioma / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008657:Metabolic Clearance Rate; D051379:Mice; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012964:Sodium / Q000378:metabolism*; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics*; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D015220:Calcium Channels; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C041470:3',4'-dichlorobenzamil; C078700:technetium tc-99m tetrofosmin; D000584:Amiloride; D017256:Technetium Tc 99m Sestamibi; D012964:Sodium; D014700:Verapamil; D005444:Flunarizine; D002118:Calcium