Metabolic design of combination therapy: use of enhanced fluorodeoxyglucose uptake caused by chemotherapy.
In order to quantify effects of an experimental chemotherapy, MCF7 cells were studied with 14C-fluorodeoxyglucose (FDG) and high-performance liquid chromatography (HPLC). Uptake measurements were performed 1 and 4 hr after the end of a therapy with hexadecylphosphocholine (HPC). A dose- and time-dependent increase of the FDG uptake after therapy was observed, with a maximum at 1 hr after therapy. These data were used to develop a new metabolic design of combination treatment. Several time-dose combinations of HPC and deoxyglucose (DOG) were analyzed for their effects on growth inhibition. The combinations using DOG in the period of pronounced enhancement of FDG uptake (1 hr after HPC treatment) were found to be the most effective with an improvement of up to 520% in growth inhibition. This metabolic design of combination treatment may also be applied in vivo, and PET can be used to optimize the time and dose schedule of the modified treatment protocol.
Haberkorn
U
U
Department of Applied Immunology, German Cancer Research Center, Heidelberg.
Reinhardt
M
M
Strauss
L G
LG
Oberdorfer
F
F
Berger
M R
MR
Altmann
A
A
Wallich
R
R
Dimitrakopoulou
A
A
van Kaick
G
G
D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003847:Deoxyglucose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004354:Drug Screening Assays, Antitumor; D019788:Fluorodeoxyglucose F18; D006801:Humans; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014055:Tomography, Emission-Computed; D014407:Tumor Cells, Cultured / Q000000981:diagnostic imaging / Q000187:drug effects
D000970:Antineoplastic Agents; D019788:Fluorodeoxyglucose F18; D010767:Phosphorylcholine; C039128:miltefosine; D003847:Deoxyglucose