Two federal agencies that monitor gene therapy trials, the Food and Drug Administration and the National Institutes of Health, want to ensure that corrective genes are not allowed to enter patients' eggs or sperm, known as germ cells.
To address such questions and to monitor gene therapy, there is a need to noninvasively locate, quantify, and longitudinally assess expression after delivery.
James Basilion (Massachusetts General Hospital, Boston, Massachusetts, USA) outlined the use of MRI as a method to detect tumors or potentially monitor gene therapy.
Noninvasive reporter gene imaging has been successfully applied to monitoring gene therapy, including gene delivery and expression mediated by retroviral [6], adenoviral [7], and oncolytic herpes viral vectors [8], [9], [10].
In this study, we sought to develop an integrative approach in which real-time tumor monitoring, gene therapy, and internal radiotherapy can be performed simultaneously.
Other approaches include: the demonstration of hypoxia, for example with radiolabelled nitroimidazoles[ 15, 16]; by showing multiple drug resistance or not as is in Tc-99m-sestaMIBI imaging[ 17]; and monitoring gene therapy with I FIAU or F FIAU, a uracil derivative[ 18].
Radioiodinated 2′-fluoro-2′-deoxy-1 β- D-arabinofuranosyl-5-iodouracil (FIAU) has been used to obtain quantitative in vivo PET images of herpes virus thymidine kinase (HSVl-tk) gene expression with superior sensitivity and resolution over that of SPECT I-radiolabeled FIAU images and also to monitor clinical gene therapy [ 26, 27].
Most importantly, our method may have potential applications in correct diagnosis of genetic disease and monitoring of gene therapy in the poverty-stricken areas.
Non-invasive imaging of transgene expression will be of great benefit in assessing organ tissue specificity as well as level and duration of transgene expression in vivo, and could therefore be very useful in validation of new delivery systems as well as in monitoring clinical gene therapy trials.
The rapid pharmacokinetics, absence of metabolism, and specific biodistribution to NIS-expressing tissues of high-specific radioactivity 18F-TFB in healthy human participants support its use as an iodide analog radiotracer for evaluation of thyroid and breast cancers and monitoring of gene therapies that employ the hNIS reporter gene.
The dual functional properties of I-hVEGF siRNA/SilenceMag in tumor therapy and imaging provide an attractive system where real time monitoring of gene delivery, gene therapy and radionuclide brachytherapy can be integrated.
