Promoter-Based Theranostics for Prostate Cancer
Technical Report,15 Sep 2014,14 Mar 2016
Johns Hopkins UniversityBaltimore Baltimore United States
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We created new molecular-genetic expression vectors for efficient, non-invasive diagnosis and targeted radiopharmaceutical therapy of prostate cancer PC. The diagnosis vector consists of the tumor-specific PEG-promoter PEG-Prom and cDNA of human chorionic gonadotropin beta chain betahCG as a reporter. We showed that transfection of the diagnostic vector to PC cells successfully produced detectable betahCG in the media by over-the-counter pregnancy kit and ELISA. We also showed that systemic, non-viral delivery of the vector to mice bearing human metastatic PC tumors produced detectable betahCG in serum and urine of the animals. The therapeutic vector has the PEG-Prom and HSV1-tk as a therapeutic gene. We also developed this therapeutic vector into clinically compatible version to comply with FDA regulation for later clinical transition. Mice with micrometastatic PC treated with sup 211At FAAU following systemic administration of the clinical vector showed significant delay in tumor development compared with untreated control. Healthy mice treated with the same therapeutic dose of sup 211At FAAU did not show any toxicity for 1 year.