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.