title: [(18)F]FDG PET monitoring of tumour response to chemotherapy: does [(18)F]FDG uptake correlate with the viable tumour cell fraction?
abstract: Because metabolic changes induced by chemotherapy precede the morphological changes, fluorine-18 fluorodeoxyglucose positron emission tomography ([(18)F]FDG PET) is thought to predict response to therapy earlier and more accurately than other modalities. To be a reliable predictor of response, changes in tumour [(18)F]FDG uptake should reflect changes in viable cell fraction, but little is known about the contribution of apoptotic and necrotic cancer cells and inflammatory tissue to the [(18)F]FDG signal. In a tumour mouse model we investigated the relation between chemotherapy-induced changes in various tumoral components and tumour uptake and size. SCID mice were subcutaneously inoculated in the right thigh with 5 x 10(6) Daudi cells. When the tumour measured 15-20 mm, Endoxan was given intravenously. At different time points [1-15 days (d1-d15) after the injection of Endoxan], ex vivo autoradiography and histopathology were performed in two mice and [(18)F]FDG uptake in the tumour and tumour size were correlated with the different cell fractions measured with flow cytometry in five mice. At d1/d3, similar reductions in [(18)F]FDG uptake and viable tumoral cell fraction were observed and these reductions preceded changes in tumour size. By d8/d10, [(18)F]FDG uptake had stabilised despite a further reduction in viable tumoral cell fraction. At these time points a major inflammatory response was observed. At d15, an increase in viable tumour cells was again observed and this was accurately predicted by an increase in [(18)F]FDG uptake, while the tumour volume remained unchanged. In contrast with variations in tumour volume, [(18)F]FDG is a good marker for chemotherapy response monitoring. However, optimal timing seems crucial since a transient increase in stromal reaction may result in overestimation of the fraction of viable cells.
authors.affiliation: Department of Nuclear Medicine, UZ Gasthuisberg, Leuven, Belgium.
authors.forename: Karoline
authors.initials: K
authors.lastname: Spaepen
authors.forename: Sigrid
authors.initials: S
authors.lastname: Stroobants
authors.forename: Patrick
authors.initials: P
authors.lastname: Dupont
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Gregor
authors.initials: G
authors.lastname: Verhoef
authors.forename: Luc
authors.initials: L
authors.lastname: Mortelmans
authors.forename: Peter
authors.initials: P
authors.lastname: Vandenberghe
authors.forename: Christine
authors.initials: C
authors.lastname: De Wolf-Peeters
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002051:Burkitt Lymphoma / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004358:Drug Therapy / Q000379:methods; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013223:Statistics as Topic; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D003520:Cyclophosphamide