Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo

• DOI: 10.1073/pnas.161091198
• Publication Date: 2002-07-26T14:34:10Z
• Authors: Michael Doubrovin; Vladimir Ponomarev; Tatiana Beresten; Julius Balatoni; William Bornmann; Ronald Finn; John Humm; Steven Larson; Michel Sadelain; Ronald Blasberg; Juri Gelovani Tju...
• Keywords: Transduction (biophysics)

A noninvasive method for molecular imaging of the activity different signal transduction pathways and expression genes in vivo would be considerable value. It aid understanding role specific have various diseases, could elucidate temporal dynamics regulation at stages disease during therapeutic interventions. We developed assessed a monitoring transcriptional activation endogenous by positron-emission tomography (PET) imaging. The HSV1-tk/GFP (TKGFP) dual reporter gene was used to monitor p53-dependent genes. retrovirus bearing Cis-p53/TKGFP system constructed which TKGFP placed under control an artificial cis-acting p53-specific enhancer. U87 glioma SaOS-2 osteosarcoma cells were transduced with this establish xenografts rats. demonstrated that DNA damage-induced up-regulation p53 correlated downstream genes, such as p21, (wild-type p53), but not (p53 -/-) cells. showed PET, [(124)I]FIAU (2'-fluoro-2'-deoxy-1-beta-d-arabinofuranosyl-5-[(124)I]iodouracil) Cis-p53TKGFP system, is sufficiently sensitive image pathway. These results confirmed independent measurements levels (e.g., p21) using conventional molecular-biological assays. PET tumor may useful assessing novel approaches.