Radiation induced vaporization of exoskeletal droplets as potential x-ray acoustic contrast agents

In vivo dosimetry is a crucial component of ensuring accurate and safe radiation therapy (RT) delivery, but many existing techniques face challenges such as low signal-to-noise ratio (SNR), which can limit their clinical applicability.

In this study, we investigate a novel contrast agent sensitive to megavoltage (MV) radiation in vitro, ultimately aiming for in vivo dosimetry.

Vaporizable exoskeletal droplets were engineered to phase-change into ultrasound-responsive microbubbles upon exposure to MV photon radiation. These droplets comprised a hydrocarbon (HC) exoskeleton doped with gold nanoparticles (GNPs) surrounding a liquid fluorocarbon (FC) core. Radiation absorbed by the GNPs induced localized heating, leading to vaporization of the FC phase. Droplet vaporization in response to clinical MV radiation was observed under a microscope at varying temperatures. Individual droplet samples were heated to temperatures ranging from 31 to 34°C, incubated for 8 min, then irradiated with a 5 × 5-cm² 10 × flattening filter free (FFF) photon beam (Varian Truebeam) at a dose rate of 24 Gy/min to measure radiation-induced vaporization. T-tests (α = 0.05) were performed comparing the number of bubbles generated from irradiated droplets with GNPs compared to irradiated droplets without GNPs and nonirradiated droplets with GNPs.

GNP-doped exoskeletal droplets exhibited enhanced vaporization in response to MV radiation compared to heating alone. Vaporization increased with radiation dose, and the dose threshold required for vaporization decreased with rising temperature. Specifically, at 31 and 34°C, the dose required to vaporize 10% of bubbles (D10%) decreased from 22 to 4 Gy, and that required to vaporize 50% of bubbles (D50%) decreased from 67.5 to 36 Gy, respectively. The activation threshold at body temperature (37°C) was extrapolated to be clinically relevant, with D10% activation estimated to be 0.41 Gy. At T = 32 to 34°C, we showed statistically significant radiation-induced vaporization of droplets with GNPs compared to non-irradiated droplets with GNPs (p-values from 0.0003 to 0.0232). Irradiation of droplets lacking GNPs did not induce notable vaporization.

GNP-doped exoskeletal droplets were demonstrated to exhibit enhanced vaporization upon exposure to clinically relevant MV x-ray radiation doses compared to thermal activation alone in the absence of radiation. This is the first step in the development of an x-ray acoustic contrast agent for dosimetry of RT in vivo.