Abstract 2138: Development of a bioluminescence imaging-guided CTC liquid biopsy procedure to identify the optimal time window for achieving superior photothermal therapy efficacy.

Abstract Global cancer burden represents one of the most significant challenges in public health. Notable concern for the mainframe therapeutic procedures is the high incidence of relapsed disease among majority patients availing those. This problem is frequently attributed to the evolving state of cancer cell dissemination, where circulating tumor cells (CTCs) begin to appear in the blood circulation. However, due to CTC enrichment requirement, high-volume blood withdrawal repeatedly during initial or follow up diagnosis, raises an ethical concern, and therefore CTC determination not integral in practice. Given the sparse nature of CTC applications in preclinical experiments using mouse model, where the total blood volume is limited to only 1.5 ml/mouse, in this study we challenged this dogma, and established a luminescence-based CTC detection method using preclinical mouse tumor models. The optimized liquid biopsy process using bioluminescence imaging-guidance allowed detection of up to two cells from as low as 100μl blood volumes, allowing us to follow the CTC surge dynamics from a very low blood volume. We examined both CTC dynamics and metastatic potential in mice bearing highly aggressive 4T1-FLuc2 and a relatively indolent ZR-75-1-Nanoluc orthotopic breast cancer models. To test the case, we further used our well-standardized photothermal therapy (PTT) procedure using gold-coated solid lipid nanomaterial (Au-SLN) and demonstrate that when PTT is performed in a temporally optimized window, the therapy application does not induce a detectable CTC flux (p< 0.05), nor distant spread of malignant tumors in the vital organs, both in highly aggressive and less aggressive breast cancer models. Imaging signal from CTC was confirmed further by molecular biomarker and transcriptomic characterization, revealing a close association of EpCAM positive CTCs with tumor aggressiveness and their metastatic propensity. These effects essentially improve mice longevity and relapse-free survival of the mice. Our findings highlight that Au-SLN mediated PTT could provide a relapse-free efficacious treatment, when performed before viable CTCs are released and underscore the importance of integrating a sensitive liquid biopsy method for monitoring metastatic risk and chance of disease relapse. Citation Format: Abhijit De, Chetna Patnaik. Development of a bioluminescence imaging-guided CTC liquid biopsy procedure to identify the optimal time window for achieving superior photothermal therapy efficacy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2138.