[18F]FDG and [18F]FLT uptake in human breast cancer cells in relation to the effects of chemotherapy: an in vitro study

Increased 2′-deoxy-2′-[18F]fluoro-D-glucose (FDG) uptake is the most commonly used marker for positron emission tomography in oncology. However, a proliferation tracer such as 3′-deoxy-3′-[18F]fluorothymidine (FLT) might be more specific for cancer. 3′-deoxy-3′-[18F]fluorothymidine uptake is dependent on thymidine kinase 1 (TK) activity, but the effects of chemotherapeutic agents are unknown. The aim of this study was to characterise FDG and FLT uptake mechanisms in vitro before and after exposure to chemotherapeutic agents. The effects of 5-fluorouracil (5-FU), doxorubicin and paclitaxel on FDG and FLT uptake were measured in MDA MB231 human breast cancer cells in relation to cell cycle distribution, expression and enzyme activity of TK-1. At IC50 concentrations, 5-FU resulted in accumulation in the G1 phase, but doxorubicin and paclitaxel induced a G2/M accumulation. Compared with untreated cells, 5-FU and doxorubicin increased TK-1 levels by >300. At 72 h, 5-FU decreased FDG uptake by 50% and FLT uptake by 54%, whereas doxorubicin increased FDG and FLT uptake by 71 and 173%, respectively. Paclitaxel increased FDG uptake with >100% after 48 h, whereas FLT uptake hardly changed. In conclusion, various chemotherapeutic agents, commonly used in the treatment of breast cancer, have different effects on the time course of uptake of both FDG and FLT in vitro. This might have implications for interpretation of clinical findings

Proton magnetic resonance metabolomic characterization of ovarian serous carcinoma effusions: chemotherapy-related effects and comparison with malignant mesothelioma and breast carcinoma

Malignant serous effusions are a common manifestation of advanced cancer, associated with significant morbidity and mortality. The aim of this study was to identify the metabolic differences between ovarian serous carcinoma effusions obtained pre- and post-chemotherapy, as well as to compare ovarian carcinoma (OC) effusions with breast carcinoma and malignant mesothelioma specimens. The supernatants of 115 effusion samples were analyzed by high-resolution magnetic resonance spectroscopy in vitro and multivariate analysis. The samples comprised pleural and peritoneal effusions from 95 OC, 10 breast carcinomas, and 10 malignant mesotheliomas. Among the OC, 8 were paired peritoneal specimens obtained pre- and post-chemotherapy from the same patient. OC had elevated levels of ketones (aceto-acetate and β-hydroxybutyrate) and lactate compared to malignant mesotheliomas and breast carcinomas, whereas the latter had more glucose, alanine, and pyruvate. Multivariate analysis of paired effusions in OC showed a significant increase in glucose and lipid levels in the post-treatment spectra (P = .039). Magnetic resonance spectroscopy is a promising technique for comprehensive and comparative studies of metabolites in malignant serous effusions, and our study shows that small metabolites associated with effusions might improve our understanding of tumor biology and disease progression and has diagnostic potential in this differential diagnosis.Copyright © 2013 Elsevier Inc. All rights reserved. This is the authors' accepted and refereed manuscript to the article

Validity of Simplified 3 '-Deoxy-3 '-[F-18]Fluorothymidine Uptake Measures for Monitoring Response to Chemotherapy in Locally Advanced Breast Cancer

Experimentele farmacotherapi