Development of Theranostic Boron-containing Agents for BNCT

Aim: In 2014, we successfully demonstrated the feasibility of combining high-intensity focused ultrasound (HIFU) with boron neutron capture therapy for the treatment of head and neck cancer (Molecular Imaging & Biology 2014;16:95-101). One of our key research directions has been the development of boron-containing nanoparticles. Notably, we showed that boron-containing gold nanoparticles modified with 61 IgG (anti-HER2 antibody) exhibited significantly enhanced tumor-targeting capabilities compared to unmodified gold nanoparticles (Colloids and Surfaces B: Biointerfaces 2019;183:110387). Additionally, we developed boron-containing nanocarriers that are trackable via magnetic resonance imaging (Int J Mol Sci. 2021;22). More recently, we synthesized carrier-free 18F-FBPA through an affinity substitution reaction (Nucl Med Biol 2023;116-117:108313), aiming to address the current clinical drug shortages through automated synthesis.

Moving forward, our research will focus on further enhancing the specificity and therapeutic efficacy of boron-containing agents for boron neutron capture therapy. We plan to explore novel boron delivery systems, investigate combination therapies with immunotherapy, and work towards the development of personalized treatment protocols that can be seamlessly integrated into clinical practice. 

Development of Radiolabeled Small Molecules for Predicting Immunotherapy Response 

Aim: Our lab previously developed radiolabeled anti-PD-L1 antibodies, enabling non-invasive imaging to assess PD-L1 expression levels in brain tumors before and after treatment. This is critical for the success of PD-L1 immune checkpoint blockade therapy, as its efficacy is likely to be limited if the patient's tumor exhibits low levels of PD-L1 expression. However, imaging has revealed that the large molecular size of the radiolabeled antibody hinders its ability to cross the blood-brain barrier (BBB). Even when the BBB is disrupted by an in situ brain tumor, large molecules still struggle to penetrate the brain. To address this, our lab is actively designing and synthesizing small-molecule PD-L1 tracers, aiming to achieve similar therapeutic effects in in situ tumors, thereby enhancing the translational potential of our research. Additionally, we are developing radiolabeled tracers targeting killer T cells and other immune cells, with the goal of establishing an immune imaging platform. This platform would allow for patient screening via imaging prior to treatment, similar to the approach used in boron neutron capture therapy. 

Development of Radiolabeled Materials for Combined Radiotherapy and Photothermal Therapy

Aim: Star-shaped gold nanoparticles are renowned for their exceptional photothermal conversion properties, making them highly effective both as nanocarriers and in treating lesions through photothermal therapy. Our lab previously developed 177Lu-labeled star-shaped gold nanoparticles, which demonstrated their accumulation in lesions through SPECT imaging and achieved therapeutic effects via emitted beta particles (Pharmaceutics 2021;13:1903). Although photothermal therapy with these nanoparticles can effectively target tumor tissues, it does not elicit a systemic immune response, limiting its efficacy against colorectal cancer. Recent studies have shown that combining this therapy with PD-L1 immune checkpoint blockade and cell therapy significantly enhances therapeutic outcomes (British Journal of Cancer 2024;130(3):406-416). Future research should aim to optimize the integration of these therapies and explore additional combination strategies to enhance systemic immune activation and overall treatment efficacy. Utilizing imaging with specific radiotracers that reflect immune responses could provide valuable insights for these advancements.