Pre-clinical validation of orthotopically-implanted pulmonary tumor by imaging with 18F-fluorothymidine-positron emission tomography/computed tomography

Anticancer Res. 2013 Nov;33(11):4741-9.

Abstract

The development of positron-emission tomography (PET) and X-ray computed tomography (CT) imaging has improved the detection of tumor burden and, in turn, pre-clinical drug development and clinical treatment. In pre-clinical drug development, clinically-relevant murine cancer models, such as orthotopic models of lung cancer, have provided an accurate representation of tumor burden in humans. However, evidence demonstrating the capability of imaging-guided evaluation of these clinically-relevant models is limited. Here, we combined (18)F-fluorothymidine (FLT)-PET/CT imaging and a murine model of human non-small cell lung cancer (NSCLC) to improve the accuracy of anticancer drug evaluation in pre-clinical studies. We found that FLT-PET/CT imaging enabled the progression of pulmonary tumors to be longitudinally monitored rather than FDG-PET/CT. Furthermore, in an efficacy study of a standard treatment of docetaxel in a murine lung cancer model, FLT-PET imaging detected the anticancer response earlier than volumetric analysis by CT imaging. We, thus, observed a relationship between the alteration of FLT signals and Ki-67 index in the pulmonary tumor during the period of chemotherapy. These results indicate that the combination of FLT-PET/CT imaging and an orthotopic NSCLC model is an effective strategy for evaluating clinical efficacy and potential of an anticancer agent during pre-clinical development.

Keywords: FLT-PET/CT; orthotopic lung cancer model.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Proliferation / drug effects
  • Dideoxynucleosides*
  • Docetaxel
  • Drug Evaluation, Preclinical*
  • Fluorodeoxyglucose F18*
  • Humans
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Nude
  • Multimodal Imaging
  • Positron-Emission Tomography*
  • Radiopharmaceuticals*
  • Taxoids / pharmacology
  • Tomography, X-Ray Computed*
  • Tumor Burden
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Dideoxynucleosides
  • Radiopharmaceuticals
  • Taxoids
  • Fluorodeoxyglucose F18
  • Docetaxel