In vitro PET evaluations in lung cancer cell lines

Anticancer Res. 2000 May-Jun;20(3A):1375-80.

Abstract

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.

Materials and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology
  • Antibiotics, Antineoplastic / therapeutic use*
  • Biological Transport
  • Bromine Radioisotopes
  • Carbon Isotopes
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Small Cell / diagnosis
  • Carcinoma, Small Cell / pathology*
  • Diagnosis, Differential
  • Diazooxonorleucine / therapeutic use*
  • Drug Monitoring / methods
  • Evaluation Studies as Topic
  • Floxuridine / analogs & derivatives
  • Floxuridine / metabolism
  • Fluorodeoxyglucose F18 / metabolism
  • Humans
  • Levodopa / metabolism
  • Lung Neoplasms / pathology*
  • Radiopharmaceuticals / metabolism
  • Tomography, Emission-Computed* / methods
  • Tumor Cells, Cultured

Substances

  • Antibiotics, Antineoplastic
  • Bromine Radioisotopes
  • Carbon Isotopes
  • Radiopharmaceuticals
  • Floxuridine
  • Diazooxonorleucine
  • Fluorodeoxyglucose F18
  • Levodopa
  • 5-bromo-1-(2-fluoro-2-deoxyribofuranosyl)uracil