The effects of radiolabelled agents used in the diagnosis and treatment of cancer, on inflammatory cytokines

Abstract

This study was conducted to determine the effects that two radiolabelled compounds have on the inflammatory cytokines and oxidative stress biomarkers in xenograft Rowett nude (RNU) rat models. Safety and efficacy are of concern when developing new compounds. There is a paucity of information on the influence of new compounds on inflammatory cytokines in combination with oxidative stress markers. Cytokines are potential markers of drug safety, and oxidative stress markers may indicate the impact of drugs on physiological processes. There is no formal reference of normal ranges of inflammatory markers. By the establishment of a baseline for preclinical safety studies, the effects of new compounds on cytokines can be quantified. The aim of this study was to determine the changes in the cytokines and anti-oxidant enzymes in tissue and serum samples in vivo (xenograft rats) after treatment with radiolabelled compounds — copper (II)- and palladium (II) chelate. Tissue was collected from RNU rats from an untreated non-xenograft group and xenograft (A549 human lung adenocarcinoma) groups: a control group and two radiolabelled compound exposed groups. Cytokines were quantified by cytometric bead array using flow cytometry. Oxidative stress biomarkers — intracellular reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and protein carbonyl (PC) — were quantified using enzymatic-based colorimetric assays. The only significant difference in the percentage composition of cytokines was seen in the tumour tissue. Compared to the xenograft control, the copper (II) chelate treatment increased the majority of the cytokines and biomarkers in the kidneys, and decreased their levels in the liver. In contrast, the palladium (II) chelate treatment had the opposite effect in both the kidneys and the liver (i.e. decrease and increase, respectively). It is evident from the large differences between treatment groups relative to the control that both cytokines and oxidative stress biomarkers can be used to elucidate the safety of new compounds in preclinical drug development studies.