Ultrasound‐guided interstitial photothermal therapy generates improved treatment responses in a 9464D model of neuroblastoma

Abstract

We describe the use of ultrasound image guidance to improve treatment outcomes when administering interstitial photothermal therapy (I‐PTT), an experimental cancer treatment modality. I‐PTT is a promising thermal therapy for tumors using intratumorally injected nanoparticle‐based photothermal agents activated by an interstitially placed laser diffuser. We hypothesized that ultrasound‐based image guidance yields improved tumor treatment outcomes in terms of tumor regression and survival by improving the accuracy of the placement of the laser fiber and nanoparticles within a tumor and facilitating more precise PTT delivery. To test this hypothesis, we assessed the effect of ultrasound‐guided I‐PTT (US I‐PTT) on neuroblastoma, an aggressive solid tumor of childhood, using the 9464D syngeneic model in C57BL/6 mice. US I‐PTT using Prussian blue nanoparticles activated by an interstitial cylindrical laser diffuser generated an equivalent in vivo thermal dose as blinded, non‐image‐guided I‐PTT (B I‐PTT). However, US I‐PTT resulted in significantly higher treatment accuracy compared to B I‐PTT, attributable to the image guidance. Importantly, this improved accuracy translated to improved treatment outcomes wherein mice treated with US I‐PTT exhibited significantly improved tumor regression, tumor‐free survival, and long‐term survival compared to mice treated with B I‐PTT. Further, histological analyses of the tumors post‐PTT confirmed the advantages conferred by US I‐PTT over B I‐PTT for tumor control. These proof‐of‐concept results demonstrate the value of using ultrasound guidance for I‐PTT treatment and the translational implications of this approach to provide a more accurate and effective treatment for neuroblastoma.