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Image-Guided Radiotherapy with Titanium Dioxide Nanoparticles Investigated in Animal Models of Pancreatic Cancer

M Moreau*, W Ngwa, Brigham and Womens Hospital, Boston, MA, Dana Farber Cancer Institute, Boston, MA, University of Massachusetts Lowell, Lowell, MA

Presentations

(Sunday, 7/12/2020)   [Eastern Time (GMT-4)]

Room: AAPM ePoster Library

Purpose: To examine the efficacy of titanium dioxide (TiO2) nanoparticles delivered from smart fiducials in the treatment of pancreatic cancer with and without radiotherapy.


Methods: Cytotoxicity was evaluated by a colony forming assay in vitro using pancreatic cancer cells namely KPC and Panc-O2 cell lines treated with and without TiO2 nanoparticles exposed to external beam radiotherapy. A small animal radiation research platform (SARRP) was used to deliver external beam radiation. Smart fiducials (SRB_TiO2) (3-5 mm length by 0.85mm diameter) were developed with a hollow core with high capacity loading of TiO2 payload. The SRB_TiO2 shell was made with biodegradable poly (lactic-co-glycolic acid) (PLGA) polymer for sustained release of the nanoparticles. First, the release of payload from the SRB_TiO2 was investigated in-vitro without radiotherapy. Second, the computed tomography (CT) image contrast of SRB_TiO2 administered using a needle into 5-7 mm diameter subcutaneous mouse tumors, generated with LSL-Kras; p53+/floxed, Pdx-cre mouse (KPC) cells was investigated in-vivo. The damage enhancement of the nanoparticles with and without radiotherapy was also investigated in-vitro.


Results: Enhanced cytotoxic effects were observed p < 0.01 for both KPC and Panc-02 cells treated with 1 µM of TiO2 nanoparticles exposed to 2 Gy of radiotherapy. Sustained release of Fluorescein payload from SRB_TiO2 implant was shown for up to 23 days. SRB_TiO2 was clearly visible in CT images like fiducials for image-guided-radiotherapy (IGRT).


Conclusion: The results demonstrate the potential of SRB_TiO2 for IGRT and therapy enhancement. These smart fiducials proffer a viable pathway to clinical translation as they could simply replace currently used fiducials, at no additional inconvenience to many cancer patients like those with pancreatic cancer.

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Keywords

Targeted Radiotherapy

Taxonomy

IM- Cone Beam CT: Biomarkers

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