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PR051/#883  Inducing a double hit to breast tumors using intra-tumoral drug delivery with local ablation
  1. Erika Chelales1,
  2. Brian Crouch2,
  3. Marlee Krieger2 and
  4. Nimmi Ramanujam1
  1. 1Duke University, Bme, Durham, USA
  2. 2Calla Health Foundation, Durham, USA

Abstract

Introduction Our objective was to demonstrate the safety and efficacy of an ablation-based drug delivery method using ethyl-cellulose ethanol (ECE) through a biodistribution study looking at chemotherapy concentrations in the heart, kidney, liver, lung, spleen, and tumor, as well as a long term survival study in a murine model of breast cancer.

Methods Biodistribution study: 4T1-Luc murine breast tumors were established in female BALB/c mice randomized to one of three groups (n=10 mice per group): ECE + local doxorubicin, ECE + systemic doxorubicin, or saline injection (no ECE) alone. Organ tissue was collected 4 hours after treatment and homogenized for analysis with IVIS imaging to quantify fluorescence from doxorubicin. Survival: 4T1-Luc bearing mice were randomized ECE with local doxorubicin or one of seven control groups (n=~10 mice per group).

Results Figure 1A-C shows the results from the biodistribution study. There were no significant differences in doxorubicin fluorescence within the heart, kidney, liver, and spleen; however, there was a significant increase in doxorubicin fluorescence within the lungs from mice treated with ECE + systemic doxorubicin. Further, there was a significant increase in doxorubicin fluorescence within the tumors of mice treated with ECE + local doxorubicin compared to ECE + systemic doxorubicin and saline control. Figure 1D-F shows the results from the suvival study. Overall survival for ECE + local doxorubicin was significantly longer than treatment with the same doxorubicin dose delivered systemically or locally.

Conclusion/Implications Chemotherapy-loaded ECE reduces systemic chemotherapeutic distribution and increases chemotherapy concentration within the tumor, translating into delayed tumor growth and improved overall survival.

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