title: Uptake of 99Tcm-nitrido dithiocarbamate complexes by tumour cells.
abstract: Uptake of radiopharmaceuticals by tumour cells may provide useful information on the biochemical characteristics of the cell, such as its drug resistance status. We have prepared a series of 99Tcm-nitrido dithiocarbamate complexes of the type [99TcmN(dtc)2] (dtc = N-R1-N-R2-dithiocarbamato, R1, R2 = Me, Me; Et, Et; Et, n-Bu; Me, CH2CH2NMe2; Me, CH2CH2NMe3+; Me, CH2COOMe), and investigated the kinetics of uptake of these complexes in several tumour cell lines. The 99Tcm-nitrido dithiocarbamate complexes were prepared by stannous reduction of [99Tcm]pertechnetate in a solution of DPTA and succinic dihydrazide followed by addition of the appropriate dithiocarbamate. The complexes were analysed by reverse-phase HPLC. The complexes were incubated with the human tumour cell lines MKN-45, H-69, H-348 and MCF-7 and with normal mixed leukocytes and erythrocytes, and the uptake and washout of the various complexes were determined at various time points. Uptake was rapid, high in some cell lines and lower in others. In general, the more lipophilic complexes showed high uptake, but the most lipophilic did not show the greatest uptake. Uptake was temperature-independent. Most of the bound activity was retained by the cells after removal of unbound tracer. The mechanism of uptake is different to that of 99Tcm-MIBI. The high and stable uptake of these complexes suggests that they may have application for in vivo tumour imaging and characterization, and further studies are required to establish their mechanisms of uptake.
authors.affiliation: Imperial Cancer Research Fund, Department of Nuclear Medicine, St Bartholomew's Hospital, West Smithfield, London, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Stalteri
authors.forename: S J
authors.initials: SJ
authors.lastname: Parrott
authors.forename: V A
authors.initials: VA
authors.lastname: Griffiths
authors.forename: J R
authors.initials: JR
authors.lastname: Dilworth
authors.forename: S J
authors.initials: SJ
authors.lastname: Mather
mesh_terms: D001693:Biological Transport, Active; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000378:metabolism; D015394:Molecular Structure; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D013859:Thiocarbamates / Q000737:chemistry / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured
chemical_list: D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D013859:Thiocarbamates; C093922:technetium Tc 99m, bis(N-ethoxy-N-ethyldithiocarbamato)nitrido-