title: [18F]FDG and [18F]FLT uptake in human breast cancer cells in relation to the effects of chemotherapy: an in vitro study.
abstract: 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.
authors.affiliation: Department of Nuclear Medicine & PET Research, VU University Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
authors.forename: W G E
authors.initials: WG
authors.lastname: Direcks
authors.forename: S C
authors.initials: SC
authors.lastname: Berndsen
authors.forename: N
authors.initials: N
authors.lastname: Proost
authors.forename: G J
authors.initials: GJ
authors.lastname: Peters
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: M D
authors.initials: MD
authors.lastname: Spreeuwenberg
authors.forename: A A
authors.initials: AA
authors.lastname: Lammertsma
authors.forename: C F M
authors.initials: CF
authors.lastname: Molthoff
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism*; D013937:Thymidine Kinase / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D019788:Fluorodeoxyglucose F18; D004317:Doxorubicin; D013937:Thymidine Kinase; D017239:Paclitaxel; D005472:Fluorouracil; D013936:Thymidine