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Purpose: To study, using phantoms made from biological tissues, the feasibility and practical challenges of monitoring the position of the radiation beam and the deposited dose by x‐ray acoustic computed tomography (XACT) during external beam radiotherapy delivery. Material and methods: A prototype XACT system with a single immersion ultrasound transducer, which was positioned around the target sample driven by a motor‐controlled rotation stage, was used to acquire the x‐ray acoustic (XA) signals produced by a medical linear accelerator (Linac) to form an XACT image of the irradiated phantom. To investigate the feasibility of XACT in tracking the position of radiation dose, a large piece of veal liver with embedded fat tissue was imaged and beam misalignments were measured. Next, we explored the sensitivity of XACT in monitoring and quantifying the delivered dose, in which a block of porcine gel was embedded with equally spaced lard cylinders and imaged. The doses on the lard cylinders modulated by physical wedges were quantified from the XACT image and were verified by comparison to measurements from radiochromic films as the gold standard. Then, to simulate how XACT can perform in a targeted tissue in the human body, a porcine gel phantom with lard cylinders covered by different materials (bone, muscle, and air gap, respectively) was also imaged. Results: The reconstructed XACT images of the phantoms show congruence with the boundaries of the beam field and the interfaces between the different tissue materials. The beam displacement from the target was tracked properly by the reconstructed XACT images. An intensity difference as small as 2.9% in delivered dose region can be measured from XACT images P = 0.02. The intensities of XACT images were highly correlated to the film measurements with an R2 better than 0.986. The expected variances of dose delivered to different target regions as a result of the difference in attenuation were successfully captured by the XACT images. Conclusions: This study validated the feasibility of XACT in accurately obtaining relative dose maps of tissue‐mimicking phantoms. XACT offers a practical method for verifying the beam position against the target and quantifying the relative dose delivered to the target during external beam radiotherapy. [ABSTRACT FROM AUTHOR]

This study presents the first in vivo and in vitro evidence of an externally controlled, predictive, MRI-based nanotheranostic agent capable of cancer cell specific targeting and killing via irreversible electroporation (IRE) in solid tumors. The rectangular-prism-shaped magnetoelectric nanoparticle is a smart nanoparticle that produces a local electric field in response to an externally applied magnetic field. When externally activated, MENPs are preferentially attracted to the highly conductive cancer cell membranes, which occurs in cancer cells because of dysregulated ion flux across their membranes. In a pancreatic adenocarcinoma murine model, MENPs activated by external magnetic fields during magnetic resonance imaging (MRI) resulted in a mean three-fold tumor volume reduction (62.3% vs 188.7%; P < .001) from a single treatment. In a longitudinal confirmatory study, 35% of mice treated with activated MENPs achieved a durable complete response for 14 weeks after one treatment. The degree of tumor volume reduction correlated with a decrease in MRI T 2 * relaxation time ( r = .351; P = .039) which suggests that MENPs have a potential to serve as a predictive nanotheranostic agent at time of treatment. There were no discernable toxicities associated with MENPs at any timepoint or on histopathological analysis of major organs. MENPs are a noninvasive alternative modality for the treatment of cancer., Summary: We investigated the theranostic capabilities of magnetoelectric nanoparticles (MENPs) combined with MRI via a murine model of pancreatic adenocarcinoma. MENPs leverage the magnetoelectric effect to convert an applied magnetic field into local electric fields, which can induce irreversible electroporation of tumor cell membranes when activated by MRI. Additionally, MENPs modulate MRI relaxivity, which can be used to predict the degree of tumor ablation. Through a pilot study (n=21) and a confirmatory study (n=27), we demonstrated that, ≥300 µg of MRI-activated MENPs significantly reduced tumor volumes, averaging a three-fold decrease as compared to controls. Furthermore, there was a direct correlation between the reduction in tumor T 2 relaxation times and tumor volume reduction, highlighting the predictive prognostic value of MENPs. Six of 17 mice in the confirmatory study's experimental arms achieved a durable complete response, showcasing the potential for durable treatment outcomes. Importantly, the administration of MENPs was not associated with any evident toxicities. This study presents the first in vivo evidence of an externally controlled, MRI-based, theranostic agent that effectively targets and treats solid tumors via irreversible electroporation while sparing normal tissues, offering a new and promising approach to cancer therapy.