The proposed work focuses on optimization and efficacy assessment of an image-guided treatment approach utilizing destruction of tissue by heat (delivered in the form of radiofrequency energy) followed by sustained release of chemotherapeutic agents from a polymer matrix. Both the delivery of heat and injection of the drug-polymer construct will be performed percutaneously under image-guidance, and the efficacy of the treatment will be evaluated in part by using functional X-ray computed tomography (CT) to study the perfusion of treated lesions. This integration of two progressive yet somewhat controversial techniques - radiofrequency ablation and local drug delivery -- creates a union that highlights the strengths and addresses the shortcomings of both approaches and remains minimally invasive to the patient. Limited preliminary experiments with this technique have shown promising results in achieving improved tumor control, but have also revealed a number of issues that need to be addressed before this treatment can be used clinically. The focus of the current study is to perfect the approach in preparation for pilot clinical studies. This will be done by achieving three primary goals: 1) Optimizing the delivery of a chemotherapeutic drug to the ablated lesion by comparing two delivery matrixes - solid polymer implants and injectable polymer gels; 2) Developing and refining the image guided percutaneous approaches of delivering the dual-mode treatment; 3) Methodically determining the long-term efficacy of the integrated treatment in vivo in a rabbit tumor model.
| Weinberg, Brent D; Krupka, Tianyi M; Haaga, John R et al. (2008) Combination of sensitizing pretreatment and radiofrequency tumor ablation: evaluation in rat model. Radiology 246:796-803 |
| Krupka, Tianyi M; Weinberg, Brent D; Wu, Hanping et al. (2007) Effect of intratumoral injection of carboplatin combined with pluronic P85 or L61 on experimental colorectal carcinoma in rats. Exp Biol Med (Maywood) 232:950-7 |
| Krupka, Tianyi M; Weinberg, Brent D; Ziats, Nicholas P et al. (2006) Injectable polymer depot combined with radiofrequency ablation for treatment of experimental carcinoma in rat. Invest Radiol 41:890-7 |
