Monitoring response to radiotherapy in human squamous cell cancer bearing nude mice: comparison of 2'-deoxy-2'-[18F]fluoro-D-glucose (FDG) and 3'-[18F]fluoro-3'-deoxythymidine (FLT)

Mol Imaging Biol. Nov-Dec 2007;9(6):340-7. doi: 10.1007/s11307-007-0104-5.

Abstract

Objective: The uptake of 3'-[18F]fluoro-3'-deoxythymidine (FLT), a proliferation marker, was measured before and during fractionated radiotherapy to evaluate the potential of FLT-positron emission tomography (PET) imaging as an indicator of tumor response compared to 2'-deoxy-2'-[18F]fluoro-D-glucose (FDG).

Materials and methods: Nude mice bearing established human head and neck xenografts (HNX-OE; nu/nu mice) were locally irradiated (three fractions/week; 22 Gy) using a 150-kVp unit. Multiple FDG- and FLT-PET scans were acquired during treatment. Tumor volume was determined regularly, and tissue was analyzed for biomarkers involved in tracer uptake.

Results: Both groups revealed a significant decline in tumor volume (P<0.01) compared to untreated tumors. For FDG as well as for FLT, a significant decline in retention was observed at day 4. For FLT, most significant decline in retention was observed at day 12; whereas, for FDG, this was already noted at day 4. Maximum decline in tumor-to-nontumor ratios (T/NT) for FDG and FLT was 42+/-18% and 49+/-16% (mean+/-SD), respectively. FLT uptake was higher then that of FDG. For FLT, statistical significant correlations were found for both tumor volume at baseline and at day 29 with T/NT and DeltaT/NT. All tumors demonstrated expression of glucose transporter-1, thymidine kinase-1, and hexokinase II. No differences were found for amount of tumor cells and necrosis at the end of treatment.

Conclusion: This new experimental in vivo model supports the promise of using FLT-PET, as with FDG-PET, to monitor response to external radiotherapy. This warrants further clinical studies to compare these two tracers especially in cancers treated with radiotherapy.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / radiotherapy*
  • Dideoxynucleosides / metabolism*
  • Disease Models, Animal
  • Fluorodeoxyglucose F18 / metabolism*
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / radiotherapy*
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Nude
  • Neoplasm Proteins / metabolism
  • Radiation Monitoring / methods*
  • Radiation Tolerance
  • Xenograft Model Antitumor Assays / methods*

Substances

  • Dideoxynucleosides
  • Neoplasm Proteins
  • Fluorodeoxyglucose F18
  • alovudine