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Nanoparticle Drones to Label, Kill and Track Circulating Tumor Cells During Radiotherapy

R Mueller1,2,3*, S Yasmin-Karim3,4 , J Hesser1,2,5,6 , W Ngwa3,4,7 , (1) University Medical Center Mannheim, Mannheim, Germany (2) Heidelberg University, Heidelberg, Germany (3) Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA (4) Harvard Medical School, Boston, MA (5) Interdisciplinary Center for Scientific Computing (IWR), Heidelberg University, Heidelberg, Germany (6) Central Institute for Computer Engineering (ZITI), Heidelberg University, Mannheim, Germany (7) University of Massachusetts Lowell, Lowell, MA


(Sunday, 7/14/2019) 4:00 PM - 5:00 PM

Room: 303

Purpose: This study investigates the potential of using high atomic number nanoparticles (NPs) for labelling, killing and tracking circulating tumor cells, which are a valuable marker to monitor treatment response and disease progression. Labelled tumor cells that escape into the blood or lymphatic vessels despite damage amplification during radiotherapy, can be non-invasively detected via photoacoustic imaging (PAI) or magnetic resonance imaging (MRI).

Methods: The labelling time from NP injection until all cells of a 2-3 cm tumor sub-volume received the minimum detectable concentration of NPs is calculated analytically using previously experimentally determined parameters for detection limit and diffusion coefficient. NPs were assumed to be released instantaneously from a sphere representing an injection site with an initial in-vivo feasible concentration of 7-30 mg/g NPs per tumor mass. Correspondingly to the analytical calculations, NPs were intratumorally injected in animal tumors and monitored using computer tomography (CT) over time.

Results: Labelling time for 2-15 nm sized gold NPs as marker for PAI ranged from 2-11 days for an initial concentration of 7 mg/g and fall within the time frame of typical radiotherapy schedules. Results show labelling within this time frame is achievable using 2 nm NP size for gadolinium NPs which provide MRI contrast. Experimental results confirm that GNPs can be localized inside the tumor over many days, consistent with radiotherapy schedules.

Conclusion: The findings in the theoretical study demonstrate the feasibility of using NPs for labelling CTCs, in-situ, for tracking those that may escape or be shed into circulation. Preliminary experimental data showed that GNPs can stay a prolonged time inside the tumor, as assumed in the theoretical study and guides further experimental validation. The development of such nanoparticle drones could provide a viable theranostic nanomedicine platform for radiation oncology.


Radiation Therapy


IM- Other (General): Nanoparticles (general)

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