Purpose Intravenous administration of indocyanine green (ICG) dye can effectively convert near infrared laser light into heat and enhance thermal injury of blood vessels; however, there is no selective uptake of ICG by the tumor compared to the other tissues which impacts the therapeutic ratio of this stratefy unless tumor uptake is somehow increases in tumor tissue. Here, we investigated the use of local hyperthermia prior to intravenous ICG administration to enhance ICG uptake in tumor tissue and thereby laser thermal ablation of solid tumors. Materials and Methods Female A/J and C3H mice with SCK or SCCVII tumors were treated with 755-nm laser light using 70 J/cm2 radiant exposures and a 3 ms pulse. The laser therapy was performed either alone or with prior intravenous administration of 4 mg/kg ICG with and without local tumor hyperthermia at 42.5°C for 60 minutes. Retention of ICG was quantified using a near-infrared animal imaging system. Tissues were examined for damage histologically. Results The ICG uptake and retention in the heated tumors was 1.23-fold greater on average compared to non-heated tumors, in both models. In SCK tumors, animals receiving either laser irradiation alone or in conjunction with ICG had 1.86 and 3.91-fold increase in tumor growth delay, respectively. The addition of local hyperthermia before ICG injection resulted in complete regression of SCK tumors. Although uptake of ICG was increased in SCCVII tumors, little change in tumor growth delay was observed. Conclusion Using local hyperthermia may improve the delivery of ICG to the tumor and thereby increase the extent of laser thermal ablation of smaller superficial malignancies that can be effectively exposed to laser therapy.

Purpose: Develop a new combination therapy consisting of cryoablation and conductive high-temperature ablation for enhanced thermal ablation of solid tumors. Methods:We have constructed an invasive probe that can be used for consecutive cryoablation and hightemperature ablation (C/HTA), with a single insertion. The C/HTA probe was tested, in Balb/c mice bearing solid 4T1 tumors, in comparison to cryoablation and high temperature ablation, only. Three days after ablation, the diameter of the ablated zone was evaluated with pathological examination.Results: The C/HTA device can be used to induce larger ablation zones, in comparison to high temperature or cryoablation alone, and at lower thermal doses and temperatures than either modality alone. Conclusions:The relatively high thermal conductivity of ice, in comparison to water and native tissue, enables rapid heating of the ice-ball that result in improved conductive high temperature ablation. The new dual thermal modality improves ablation outcomes at lower thermal doses in comparison to a single ablation modality.

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