Cyclopentadecanolide (CPDL) emulsions markedly lower the threshold temperature required to thermally ablate solid tissues. The proposed study will test the hypothesis that targeted delivery of CPDL into liver tumors will preferentially sensitize them to thermal ablation at temperatures of 44-55oC and that this CPDL-mediated reduced temperature thermal ablation (CPDL-RTTA) strategy will result in safer and more effective thermal ablation of liver tumors with improved sparing of normal liver tissue. Experiments will be performed using the rat Walker 256 liver tumor model.
Specific aim one is to identify the most effective means for localizing delivery of effective doses of CPDL to liver tumors and to confirm that the prescribed CPDL dose has been delivered to tumors before initiating thermal ablation.
The second aim i s to demonstrate that CPDL-RTTA increases tumor ablation volume, can overcome the vascular heat sink effect, and will improve the ability to establish local tumor control. If this study is successful the developed treatment strategies can be directed towards treating patients that are currently ineligible for thermal ablation therapy for their liver tumors. Thermal ablation will then have broader applicability and utility as a treatment for establishing local tumor control, downstaging liver tumors so that resection or liver transplant become treatment options, or palliating advanced disease to improve quality of life.
The objective of this proposal is to develop a better procedure for thermally ablating human hepatocellular carcinoma (HCC) and other liver tumors such that tumor killing is improved while more normal tissue is spared and remains functional. This will be accomplished by targeting delivery of a chemical emulsion (active ingredient cyclopentadecanolide (CPDL)) that markedly lowers the temperature threshold required to ablate the tumor. Effective tumor ablation will be performed using temperatures between 45-55oC, which will not harm normal liver tissues since they will not have received the thermal sensitizing CPDL. If successful, the CPDL procedure will improve tumor ablation efficacy and should make tumor thermal ablation available to patients that are currently excluded because their liver tumors are too numerous and/or massive.
|Penthala, Narsimha Reddy; Janganati, Venumadhav; Alpe, Terri L et al. (2016) N-[(11)CH3]Dimethylaminoparthenolide (DMAPT) uptake into orthotopic 9LSF glioblastoma tumors in the rat. Bioorg Med Chem Lett 26:5883-5886|