UPTAKE OF TC-99(M)-NITRIDO DITHIOCARBAMATE COMPLEXES BY TUMOR-CELLS

Uptake of radiopharmaceuticals by tumour cells may provide useful info rmation on the biochemical characteristics of the cell, such as its dr ug resistance status. We have prepared a series of Tc-99(m)-nitrido di thiocarbamate complexes of the type [(TcN)-Tc-99-N-m(dtC)(2)] (dtc = N -R-1-N-R-2-dithiocarbamato, R-1, R-2 = Me, Me; Et, Et; Et, n-Bu; Me, C H2CH2NMe2; Me, CH2CH2Me3+; Me, CH2COOMe), and investigated the kinetic s of uptake of these complexes in several tumour cell lines. The Tc-99 (m)-nitrido dithiocarbamate complexes were prepared by stannous reduct ion of [Tc-99(m)]pertechnetate in a solution of DPTA and succinic dihy drazide followed by addition of the appropriate dithiocarbamate. The c omplexes were analysed by reverse-phase HPLC. The complexes were incub ated with the human tumour cell Lines MKN-45, H-69, H-348 and MCF-7 an d with normal mixed leukocytes and erythrocytes, and the uptake and wa shout of the various complexes were determined at various time points. Uptake was rapid, high in some cell lines and lower in others. In gen eral, the more lipophilic complexes Showed high uptake; but the most l ipophilic did not show the greatest uptake. Uptake was temperature-ind ependent. Most of the bound activity was retained by the cells after r emoval of unbound tracer. Thr mechanism of uptake is different to that of Tc-99(m)-MIBI. The high and stable uptake of these complexes sugge sts that they may have application for in vivo tumour imaging and char acterization, and further studies are required to establish their mech anisms of uptake.