Dose-dependent uptake of 3'-deoxy-3'-[(18) F]fluorothymidine by the bowel after total-body irradiation

Mol Imaging Biol. 2014 Dec;16(6):846-53. doi: 10.1007/s11307-014-0755-y.

Abstract

Purpose: The aim of this study is to non-invasively assess early, irradiation-induced normal tissue alterations via metabolic imaging with 3'-deoxy-3'-[(18) F]fluorothymidine ([(18) F]FLT).

Procedures: Twenty-nine male C57BL/6 mice were investigated by [(18) F]FLT positron emission tomography for 7 days after total body irradiation (1, 4, and 8 Gy) versus 'sham' irradiation (0 Gy). Target/background ratios were determined. The imaging results were validated by histology and immunohistochemistry (Thymidine kinase 1, Ki-67).

Results: [(18) F]FLT demonstrated a dose-dependent intestinal accumulation post irradiation. Mean target/background ratio (±standard error) 0 Gy: 1.4 (0.2), 1 Gy: 1.7 (0.1), 4 Gy: 3.1 (0.3), 8 Gy: 4.2 (0.6). Receiver operating characteristic analysis (area under the curve, p value): 0 vs. 1 Gy: 0.81, 0.049; 0 vs. 4 Gy: 1.0, 0.0016; and 0 vs. 8 Gy: 1.0, 0.0020. Immunohistochemistry confirmed the results.

Conclusions: [(18) F]FLT seems to provide dose-dependent information on radiation-induced proliferation in the bowel. This opens the perspective for monitoring therapy-related side-effects as well as assessing, e.g., radiation accident victims.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dideoxynucleosides / chemistry
  • Dideoxynucleosides / pharmacokinetics*
  • Dose-Response Relationship, Radiation
  • Immunohistochemistry
  • Intestine, Large / chemistry
  • Intestine, Large / metabolism*
  • Intestine, Large / radiation effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics*
  • Whole-Body Irradiation / methods*

Substances

  • Dideoxynucleosides
  • Radiopharmaceuticals
  • alovudine