Cholangiocarcinoma: molecular imaging-guided radiofrequency hyperthermia-enhanced intratumoral herpes simplex virus thymidine kinase gene therapy.

We investigated the feasibility of using radiofrequency hyperthermia (RFH) to enhance green fluorescent protein (GFP)/herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV) gene therapy of cholangiocarcinoma. Cholangiocarcinoma cells and mice with cholangiocarcinoma were treated by (i) GFP/HSV-TK/plasmid combined with RFH at 42°C, followed by ganciclovir administration; (ii) HSV-TK alone; (iii) RFH alone; and (iv) saline. The therapeutic effects among different treatments were evaluated by bioluminescent optical imaging and ultrasound imaging. For the technical validation, GFP/HSV-TK/plasmid was intrabiliarily injected into pig common bile duct (CBD) walls using a needle-integrated balloon catheter with or without RFH enhancement. GFP gene expression was evaluated by optical imaging, which was correlated with histology. The results show that combination therapy of HSV-TK plus RFH significantly induced lower cell viabilities and decreased bioluminescence signals compared the other three groups, which were further confirmed by the tumor volume decrease with combination therapy, as measured by ultrasound imaging. Optical imaging of CBD tissues demonstrated an increased GFP expression in the group with RFH enhancement, compared that with non-RFH treatment. We concluded that intratumoral RFH can enhance the therapeutic effect of GFP/HSV-TK/plasmid on cholangiocarcinoma, which may open new avenues for effective treatment of this deadly disease.