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


CONCLUSIONS
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.
Xu
Wen-gui
WG
Key Laboratory of Breast Cancer Prevention & Therapy, Tianjin Medical University, Ministry of Education, Tianjin 300060, China. wenguixy@tom.com
Dai
Dong
D
Fang
Na
N
Song
Xiu-yu
XY
Wang
Jian
J
Zhu
Yan-jia
YJ
Men
Xiao-yuan
XY
D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000235:genetics; D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D005462:Fluorine Radioisotopes; D017930:Genes, Reporter; D015316:Genetic Therapy; D006147:Guanine / Q000031:analogs & derivatives; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography
C113308:9-(4-fluoro-3-hydroxymethylbutyl)guanine; D005462:Fluorine Radioisotopes; D006147:Guanine