Studies of in vivo labelling of nucleic acids with 99mTc complexes. First results: uptake in cultured cells.

99mTc labelled nucleobases are expected to be precursors for in vivo radioactive labelling of DNA. This offers the possibility for visualization of tumours developing in surroundings of non-dividing tissue as e.g. brain.
The aim of the study was achieve uptake of 99mTc complexes of derivatized nucleic acid precursors, especially mercaptoamide functionalized uracil derivatives, into proliferating cells.
The 99mTc complexes were prepared by ligand exchange on 99mTc(V) gluconate both as mixed ligand complexes according to the "3+1 principle" and as complexes formed by (MAG)_n chelators coupled to nucleobases.
Uptake of 7 selected compounds into the crude cytosolic and nuclear fractions of cultured V79 cells was checked. Pulse labelling for 4 hrs showed cellular uptake of some compounds. Best results were about 20% cellular uptake, and thereof up to 40% in the nuclear fraction. The corresponding results with ³HTdR controls were 20% and 75% respectively.
Postincubation experiments showed an increase of the percent 99mTc radioactivity in the nuclear fraction by a factor of 2. This means integration of the complex in the nucleus from the pool present in the cytosol after the initial incubation. No radioactivity was released into the postincubation medium.
The results are encouraging, making evident that complex compounds of this kind can be taken up into the cell nucleus.