Application of α-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.

Multiparametric assessment of acute and subacute ischemic neuronal damage: A small animal positron emission tomography study with rat photochemically induced thrombosis model

“…Although damaged neuronal areas are expected to be detected from lower [ 18 F]FDG uptake than that in intact area, several limitations of [ 18 F]FDG, such as uptake by foci of infection and/or inflammation (Kubota et al, 1992; Yamada et al, 1995), might provide incorrect results of neuronal damage. In tumor imaging with PET, it is well known that [ 18 F]FDG exhibits a lower sensitivity and/or specificity for the assessment of chemotherapy (Haberkorn et al, 1997; Schaider et al, 1996) and radiation therapy (Murayama et al, 2009; Sugiyama et al, 2004), all of which induce inflammation response in tissues. In contrast to tumor imaging, little evidence has been reported on how inflammatory activation in the brains affected by neurodegenerative diseases influences the results of [ 18 F]FDG‐PET.…”

Toxicity, Antitumor and Chemosensitizing Effects of 3-Chloroprocainamide

“…A number of benzamide derivatives have been shown to possess the properties of antitumor activity or sensitization of cytotoxicity induced by chemo-or radiotherapies both in vitro and in vivo (7,15,(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). The mechanism of action that has so far been attributed to this class of agents can be conveniently divided into two pharmacological categories: namely (a) the non-N-substituted benzamides and nicotinamides which can alter tumor blood flow and thus increase DNA damage and sensitizes (32) and (b) the N-substituted benzamides and nicotinamides which can inhibit DNA repair, increase DNA damage, induce apoptosis and thereby sensitize (12, 13.…”

Radiohalogenated nonnatural amino acids as PET and SPECT tumor imaging agents

“…Several groups have used radiolabeled AIB for tumor imaging in animal models of brain and systemic tumors, including rodents with implanted glioma, colon, melanoma, and prostate tumors as well canines with spontaneously occurring tumors . In these studies, AIB generally demonstrated good tumor imaging properties, although the uptake in the spontaneous canine tumors was variable.…”