Noninvasive assessment of regulable transferred-p53 gene expression and evaluation of therapeutic response with FDG-PET in tumor model.
The use of tumor-suppressor gene p53 as an anticancer therapeutic has been vigorously investigated. However, progress has met with limited success to date. Some major drawbacks are the difficulty in achieving controllable and efficient gene transfer as well as in analyzing the transferred gene expression in real time and the treatment response in a timely manner. Thus, development of novel gene transfer vector with a regulative gene expression system coupled with the reporter gene, by which transgene can be monitored simultaneously, is critical. Moreover, noninvasive imaging-based assessment of the therapeutic response to exogenous wild-type p53 gene transfer is crucial for refining treatment protocols. In this study, as a simple preclinical model, we constructed a doxycycline-regulated bidirectional vector harboring a reporter gene encoding red fluorescence protein and p53. Then, we determined the controllable and simultaneously coordinated expression of both proteins and the p53-mediated anticancer effects in vitro and in vivo. Next, we observed that cells or tumors with induced p53 overexpression exhibited decreased uptake of [(14)C]FDG in cellular assay and [(18)F]FDG in positron emission tomography (PET) imaging. Thus, by coupling with bidirectional vector, controllable p53 transfer was achieved and the capability of fluoro-2-deoxy-D-glucose (FDG)-PET to assess the therapeutic response to p53 gene therapy was evidently confirmed, which may have an impact on the improvement of p53 gene therapy.
Aung
W
W
Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan. winn@nirs.go.jp
Hasegawa
S
S
Koshikawa-Yano
M
M
Tsuji
A B
AB
Sogawa
C
C
Sudo
H
H
Sugyo
A
A
Koizumi
M
M
Furukawa
T
T
Saga
T
T
D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism / Q000493:pharmacokinetics*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000378:metabolism / Q000493:pharmacokinetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D000097573:Red Fluorescent Protein
D019788:Fluorodeoxyglucose F18; D008164:Luminescent Proteins; D019275:Radiopharmaceuticals; D016159:Tumor Suppressor Protein p53; D000097573:Red Fluorescent Protein