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Image-Guidance and Conformal Dose-Painting with Nanoparticles in Hydrogel

W Swanson1*, S Yasmin-Karim2,3,4, R Mueller3,4,5,6 , M Moreau1,3, K Decosmo7, W Ngwa1,2,3,4, (1) University of Massachusetts Lowell, Lowell, MA, (2) Harvard Medical School, Boston, MA, (3) Dana Farber Cancer Institute, Boston, MA, (4) Brigham and Womens Hospital, Boston, MA, (5) University Medical Center Mannheim, Mannheim, Germany, (6) Heidelberg University, Heidelberg, Germany, (7) Northeastern University, Boston, MA


(Sunday, 7/14/2019) 5:00 PM - 6:00 PM

Room: 302

Purpose: Traditional solid fiducial markers assist image registration for image-guided-radiotherapy (IGRT), but otherwise have minimal function and can contribute to tissue inflammation. Additionally, they can migrate, reducing the certainty of accurate patient alignment. This investigation is a development of an alternative multifunctional registration marker using gold nanoparticles (AuNPs) suspended in a sodium-alginate hydrogel (ALG). Previous work has shown promise in the use of AuNPs for dose conforming by exploiting the photoelectric effect creating a dose-enhancement-factor (DEF) in the AuNP-occupied region. The ALG localizes the AuNPs within the interstitial space of the tumor, increasing radiopacity of the tumor volume, by that acting as its own fiducial marker, and contributing dose-enhancement to the tumor.

Methods: A cohort of 12 mice were implanted with pancreatic cancer cells subcutaneously. Once tumors developed, they were treated with combinations of radiotherapy, phosphate-buffered saline (PBS)-suspended AuNPs, and ALG-suspended AuNPs. To explore additional applications for the highly-conformed dose-enhancement, radiotherapy treated mice were also injected with antibody CD40 (AbCD40) to provoke an immune response. Tumor sizes and mouse survival rates were monitored to generate outcome data and computed tomography (CT) images were taken to track AuNP localization.

Results: CT images showed significant visibility of the AuNPs inside the tumor with minimal diffusion from injection site. The ALG-suspended AuNPs showed localized pixel intensity four times greater than that from the PBS-suspension relative to the surrounding tissue Preliminary therapeutic enhancement data warrants protocol optimization for further investigation.

Conclusion: The application of ALG-suspended AuNPs has proven valuable for CT visibility. This warrants further study for ALG concentration and AuNP size optimization to enable fine diffusion control and maximizing dose-enhancement to the tumor volume. A large mouse cohort is planned for an in-depth investigation to determine therapeutic potential of ALG-suspended AuNPs beyond the application of increasing radiopacity.


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