From: HubMed - cancer <rssfwd@rssfwd.com>
Date: Thu, Aug 21, 2008 at 9:30 PM
Subject: Phase I Study of Noninvasive Imaging of Adenovirus-mediated Gene Expression in the Human Prostate.
To: mesothelioma77@gmail.com
[1]Mol Ther. 2008 Aug 19;
Barton KN, Stricker H, Brown SL, Elshaikh M, Aref I, Lu M, Pegg J, Zhang Y, Karvelis KC, Siddiqui F, Kim JH, Freytag SO, Movsas B
To monitor noninvasively potentially therapeutic adenoviruses for cancer, we have developed a methodology based on the sodium iodide symporter (NIS). Men with clinically localized prostate cancer were administered an intraprostatic injection of a replication-competent adenovirus, Ad5-yCD/utTK(SR39)rep-hNIS, armed with two suicide genes and the NIS gene. NIS gene expression (GE) was imaged noninvasively by uptake of Na(99 m)TcO(4) in infected cells using single photon emission-computed tomography (SPECT). The investigational therapy was safe with 98% of the adverse events being grade 1 or 2. GE was detected in the prostate in seven of nine (78%) patients at 1 x 10(12) virus particles (vp) but not at 1 x 10(11) vp. Volume and total amount of GE was quantified by SPECT. Following injection of 1 x 10(12) vp in 1 cm(3), GE volume (GEV) increased to a mean of 6.6 cm(3), representing, on average, 18% of the total prostate volume. GEV and intensity peaked 1-2 days after the adenovirus injection and was detectable in the prostate up to 7 days. Whole-body imaging demonstrated intraprostatic gene expression, and there was no evidence of extraprostatic dissemination of the adenovirus by SPECT imaging. The results demonstrate that noninvasive imaging of adenovirus-mediated gene therapy in humans is feasible and safe.Molecular Therapy (2008); doi:10.1038/mt.2008.172.
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Source: http://www.hubmed.org/display.cgi?uids=18714306
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