Comparison of [18F]-tracers in various experimental tumor models by PET imaging and identification of an early response biomarker for the novel microtubule stabilizer patupilone

Mol Imaging Biol. 2009 Sep-Oct;11(5):308-21. doi: 10.1007/s11307-009-0216-1. Epub 2009 May 22.

Abstract

Purpose: The suitability of [18F]FDG, [18F]FLT, [18F]FET, and [18F]FCH as non-invasive positron emission tomography (PET) biomarkers for monitoring response to chemotherapy was analyzed in various experimental tumor models.

Procedures: Tracer uptake into three syngeneic rodent tumor models and ten human xenograft models was evaluated using semiquantitative analysis of small-animal PET data. Murine RIF-1 fibrosarcomas and [18F]FLT were selected to monitor the effects of the novel cytotoxic patupilone.

Results: Except [18F]FCH, all tracers provided good tumor visualization. Highest [18F]FDG uptake was identified in syngeneic tumors. Xenograft models, however, showed low [18F]FDG SUVs and were better visualized by [18F]FLT. Monitoring the effects of patupilone on [18F]FLT uptake in RIF-1 tumors revealed a significant decrease of tracer uptake after 24 h, which strongly negatively correlated with apoptosis.

Conclusion: [18F]FLT PET of experimental tumors is a viable complement to [18F]FDG for preclinical drug development. [18F]FLT may be an excellent biomarker for patupilone-induced apoptosis.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Choline / analogs & derivatives
  • Choline / pharmacokinetics
  • Dideoxynucleosides / pharmacokinetics
  • Disease Models, Animal
  • Epothilones / pharmacology*
  • Female
  • Fluorine Radioisotopes* / pharmacokinetics
  • Fluorodeoxyglucose F18 / pharmacokinetics
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms / diagnostic imaging*
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals* / pharmacokinetics
  • Rats
  • Reproducibility of Results
  • Transplantation, Heterologous
  • Tubulin Modulators / pharmacology
  • Tyrosine / analogs & derivatives
  • Tyrosine / pharmacokinetics
  • Whole Body Imaging / methods

Substances

  • Antineoplastic Agents
  • Dideoxynucleosides
  • Epothilones
  • Fluorine Radioisotopes
  • O-(18F)fluoromethyl-L-tyrosine
  • Radiopharmaceuticals
  • Tubulin Modulators
  • Fluorodeoxyglucose F18
  • Tyrosine
  • fluorocholine
  • Choline
  • alovudine
  • epothilone B