Application of alpha-aminoisobutyric acid, L-methionine, thymidine and 2-fluoro-2-deoxy-D-glucose to monitor effects of chemotherapy in a human colon carcinoma cell line

Abstract

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.