[Molecular imaging for PET-CT reporter gene in breast adenocarcinoma (HSV1-tk) of subcutaneous xenografts in living nude mice]

Zhonghua Yi Xue Za Zhi. 2009 Dec 29;89(48):3420-4.
[Article in Chinese]

Abstract

Objective: To study the in vitro accumulation of (18)F-FHBG, its in vivo distribution and (18)F-FHBG PET-CT imaging for reporter gene (HSV1-tk) in nude mice with a xenograft of breast adenocarcinoma.

Methods: The in vitro uptake of (18)F-FHBG in tumor cells of T47D and T47D-tk and the distribution of (18)F-FHBG in normal Kunming mice and nude mice with breast adenocarcinoma xenograft were detected by well-type gamma counter. Reporter gene PET-CT imaging with (18)F-FHBG was performed in nude mice with a xenograft of breast adenocarcinoma. And the expression location of HSV1-tk gene could be monitored by observing the in vitro and in vivo accumulation of (18)F-FHBG.

Results: The in vitro uptake of (18)F-FHBG in T47D-tk cells (143.67 dpm/10(4) +/- 5.82 dpm/10(4) cells) was significantly higher than that in T47D cells (2.23 dpm/10(4) +/- 0.23 dpm/10(4) cells) at 60 and 120 min post-injection (P < 0.001) and reaches a plateau at 60 min. In normal Kunming mice, (18)F-FHBG was mainly distributed in liver, intestine, kidney and bladder while there was no obvious radioactive accumulation in brain. (18)F-FHBG accumulated at a significantly higher level in T47D-tk tumors than in T47D tumors and its accumulation yielded the best image effect at 2 h by PET-CT imaging in nude mice.

Conclusion: The in vitro uptake of (18)F-FHBG in T47D-tk cells is significantly higher than that in T47D cells. (18)F-FHBG is mainly excreted by digestive tract and urinary tract in mice. It agrees with the expression pattern of HSV1-tk gene. (18)F-FHBG can determine the localization of HSV1-tk gene expression in an efficient way. This study will offer a monitoring method and scientific base for (18)F-FHBG reporter gene imaging and HSV1-tk gene therapy in tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnostic imaging*
  • Adenocarcinoma / genetics
  • Animals
  • Breast Neoplasms / diagnostic imaging*
  • Breast Neoplasms / genetics
  • Cell Line, Tumor
  • Female
  • Fluorine Radioisotopes
  • Genes, Reporter*
  • Genetic Therapy
  • Guanine / analogs & derivatives
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred Strains
  • Mice, Nude
  • Neoplasm Transplantation
  • Positron-Emission Tomography*

Substances

  • 9-(4-fluoro-3-hydroxymethylbutyl)guanine
  • Fluorine Radioisotopes
  • Guanine