Abstract 585: Treatment of squamous cell carcinoma with ultrasound and microbubble mediated gene therapy

• Published in: Cancer research (Chicago, Ill.) Ill.), 2010-04, Vol.70 (8_Supplement), p.585-585
• Main Authors: Carson, Andrew R., Mctiernan, Charles F., Lavery, Linda, Schwartz, Abigail, Grata, Michelle, Leng, Xiaoping, Wang, Jianjun, Chen, Xucai, Modzelewski, Ruth A., Villanueva, Flordeliza S.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM10-585

Background: Ultrasound contrast agents are gas-filled microbubbles (MB) that can be induced to vibrate or cavitate in an ultrasound field. When the MB are loaded with genes and systemically injected, ultrasound-targeted MB destruction (UTMD) has been shown to facilitate focused delivery and transduction of genes to the target site. An experimental model of mouse squamous cell carcinoma was used to test the hypothesis that delivery of a suicide gene via UTMD would slow tumor growth. Methods: Lipid based perfluorobutane gas-filled MBs (2 μm diameter) were synthesized incorporating a cationic phospholipid to enable loading with DNA (100 ug per 109 MB). DNA loading was confirmed using electrophoresis and DNAseI challenge. Primary cultured mouse squamous carcinoma cells were subcutaneously injected into mice. 3-5 days after cell injection, mice were intravenously infused over 30 min with MB (5 × 108) loaded with plasmids containing reporter genes GFP (n = 3) or luciferase (n = 6). During MB infusion, ultrasound (1.3MHz) was intermittently delivered using a clinical scanner at high acoustic power, with simultaneous ultrasound imaging used to confirm MB destruction within the tumor. To assess the therapeutic potential of the system, tumors were allowed to grow to 100 µl, and MB (5 × 108) loaded with plasmid containing either the suicide gene thymidine kinase (TK) (n = 6) or GFP control (n = 6) was given to separate groups of mice along with ultrasound treatment. Gancyclovir was administered 3 days after UTMD and tumors were serially measured until they were 2ml in volume, after which animals were euthanized and tissue harvested for histology. Results: UTMD-mediated delivery of reporter genes resulted in tumor expression of luciferase (1568 RLU/min/mg) and GFP (