In vitro PET evaluations in lung cancer cell lines.
One purpose of the study was to explore the PET tracer 11C-L-DOPA for the discrimination between small-cell lung cancer (SCLC) and non small-cell lung cancer (NSCLC). A further aim was to explore the potential antitumoral effects of 6-diazo-5-oxy-L-norleucine (DON) and the use of a PET proliferation marker for the evaluation.


METHODS
Four lung cancer and one endocrine tumour cell line (BON) were cultured as monolayer. The uptake of 5-[76Br]-bromo-2-fluoro-deoxyuridine (76Br-BFU), [11C]-L-DOPA (11C-DOPA) and [18F]-fluorodeoxyglucose (18FDG) were evaluated. The effects of specific enzyme inhibitors affecting the DOPA metabolism were explored. The effect of DON on proliferation and uptake of 76Br-BFU were assessed.


RESULTS
All cell types showed a measurable uptake of 11C-DORA, with slightly lower values in lung cancer. There were no clear differences between SCLC and NSCLC. The addition of COMT inhibitor induced a significantly increased uptake of the tracer in BON cells, but not in lung cancer cells. DON significantly reduced the proliferation in all cell lines. The 76Br-BFU uptake was reduced markedly in all cell lines during DOn treatment.


CONCLUSIONS
11C-DOPA failed to distinguish between SCLC and NSCLC. DON showed strong antiproliferative effects which might motivate renewed interest in this drug for clinical cancer treatment. PET with 76Br-BFU might be used for treatment evaluation.
Department of Oncology, University Hospital, Uppsala, Sweden.
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Xing
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Wu
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Brodin
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Fasth
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Långström
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Bergström
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D001692:Biological Transport; D001967:Bromine Radioisotopes; D002247:Carbon Isotopes; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000473:pathology*; D018288:Carcinoma, Small Cell / Q000175:diagnosis / Q000473:pathology*; D003937:Diagnosis, Differential; D003980:Diazooxonorleucine / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods; D005069:Evaluation Studies as Topic; D005467:Floxuridine / Q000031:analogs & derivatives / Q000378:metabolism; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D006801:Humans; D007980:Levodopa / Q000378:metabolism; D008175:Lung Neoplasms / Q000473:pathology*; D019275:Radiopharmaceuticals / Q000378:metabolism; D014055:Tomography, Emission-Computed / Q000379:methods; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D001967:Bromine Radioisotopes; D002247:Carbon Isotopes; D019275:Radiopharmaceuticals; D005467:Floxuridine; D003980:Diazooxonorleucine; D019788:Fluorodeoxyglucose F18; D007980:Levodopa; C059969:5-bromo-1-(2-fluoro-2-deoxyribofuranosyl)uracil