Up to 4 h
after treatment of human SW 707 colon
carcinoma cells with the
antineoplastic drug 4-amino-N-(2'-aminophenyl)-benzamide (
GOE 1734,
dinaline), the effects of tumour cell metabolism and proliferation were examined in vitro. Four tracers which can be labelled with
isotopes suitable for positron emission tomography (PET) were used for this purpose:
alpha-aminoisobutyric acid (AIB) and
methionine to study changes in
amino acid transport and
protein synthesis,
thymidine to observe changes in tumour proliferation and
2-fluoro-2-deoxy-D-glucose (FDG) to estimate
glucose metabolism.
Dinaline showed an inhibition of the
sodium-dependent and -independent uptake of AIB. The
methionine uptake was found to increase shortly after
therapy.
Thymidine incorporation into
DNA was impaired and the FDG uptake showed a maximally 2.2-fold enhancement. Inhibition of AIB uptake suggests changes in
amino acid transport, whereas increased uptake of
methionine and FDG points to an enhancement of
protein synthesis and glycolysis caused by repair mechanisms. The
cytostatic and antiproliferative effect of
dinaline, observed in cell growth curves, could be demonstrated by the impaired
thymidine incorporation into
DNA. This study demonstrates that in vitro screening with radiotracers suitable for PET can help to clarify effects of new
antineoplastic substances on tumour cell metabolism. These data may be applied to choose the appropriate time schedule for monitoring
therapeutic effects on tumour tissue.