Abstract 5777: A guidance platform for nanoparticle mediated photothermal therapy for solid tumors

Introduction Nanoparticle-mediated Photothermal therapy (PTT) is an option for treating solid tumors with low cost and toxicity. Except for a limited set of cancers, PTT in general has not seen widespread clinical adoption, due in part to lack of effective treatment guidance technology. Recent clinical trials here and elsewhere investigating MRI-guided PTT have highlighted 3 critical requirements, including visualization of (1) tumor nanoparticle uptake, (2) temperature distribution during PTT and (3) treatment effect. These trials also highlighted shortcomings of MRI guidance, including high cost and limited access, complexity, speed and indirect functionality, so there is a need for novel direct, real-time PTT-guidance technology. Methods and Results We have designed and constructed a PTT-guidance platform based on hand-held multispectral photoacoustic (PA) tomography enabled by an in-house built frequency-optimized acoustic sensor array designed specifically to capture volumetric PA signals at depths of up to several cm. This is able to quantitatively image bulk-tissue endogenous and exogeneous contrast, including nanoparticle distribution in tumor (Requirement #1). In addition, this platform provides highly sensitive deep-tissue temperature mapping through the temperature dependence of the tissue Gruneisen parameter, matching or exceeding MRI-based thermometry but with direct, real-time precision in an ergonomic hand-held configuration (Requirement #2). Integration of a custom-built diffuse optical tomography (DOT) module into the PAI platform provides measures of the time-dependent tissue optical properties during PTT, particularly scattering that is known to increase 2 to 3-fold with coagulation above ∼55oC. Thereby, it provides immediate feedback on the size and location of the photocoagulated lesion (Requirement #3). Results of in vivo and pre-clinical validation studies are presented, showing nanoparticle injection and distribution in tissues, PA thermal mapping and DOT-based proof-of-principle monitoring of PTT treatments in patients with localized prostate cancer. Conclusions These studies indicate that we can provide the three needed functionalities for PTT guidance and that, for the first time, this can be done on a spatial scale relevant to clinical translation. This work is supported by the Terry Fox Research Institute and the Canadian Cancer Society. Citation Format: Ivan Kosik, Robert Weersink, Margarete Akens, Fumi Yokote, Sangeet Ghai, Gang Zheng, Brian Wilson. A guidance platform for nanoparticle mediated photothermal therapy for solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5777.