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Chemical design of nir-i and nir-ii dyes for fluorescence-guided surgery of non-small cell lung cancer Ritesh K Isuri
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Isuri, Ritesh K., author.
- Language:
- English
- Subjects (All):
- Chemistry.
- Biomedical engineering.
- Oncology.
- Medical imaging.
- Surgery.
- 0485.
- 0576.
- 0541.
- 0574.
- 0992.
- Local Subjects:
- Chemistry.
- Biomedical engineering.
- Oncology.
- Medical imaging.
- Surgery.
- 0485.
- 0576.
- 0541.
- 0574.
- 0992.
- Genre:
- Academic theses
- Physical Description:
- 1 online resource (290 pages)
- Contained In:
- Dissertations Abstracts International 87-12B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2026
- Language Note:
- English
- Summary:
- Fluorescence-guided surgery (FGS) is a powerful approach to improve intraoperative tumor visualization; however, current clinical fluorophores are limited by poor specificity, insufficient contrast, and an inability to capture tumor heterogeneity. This dissertation presents the design, validation, and translational evaluation of complementary imaging strategies targeting enzyme activity, metabolic reprogramming, and receptor expression in non-small cell lung cancer (NSCLC). An activatable probe, DDAO-arachidonate (DDAO-A), was developed to report cytosolic phospholipase A2 (cPLA2) activity. DDAO-A showed selective activation in vitro and strong correlation with cPLA2 expression, with robust tumor contrast across species (TNR ∼4.3 in murine and human NSCLC). Liposomal formulations enhanced in vivo performance, and ex vivo tumor painting enabled detection of metastatic lymph nodes and occult tumor regions, demonstrating clinical relevance. To improve optical performance, a novel class of NIR-II quinolinium fluorophores was developed, with JAM317 identified as a lead compound targeting choline kinase α (ChoKα). Emitting at 1002 nm, JAM317 enabled deeper tissue imaging with reduced autofluorescence. It demonstrated target-dependent activity, increasing tumor contrast over time in vivo (TNR ∼10-13) and achieving high contrast across human, canine, and glioma specimens (TNR >12), with strong correlation to ChoKα expression. To enhance clinical translation, indocyanine green (ICG)-based folate conjugates were synthesized for folate receptor α (FRα) targeting. Lead compounds ICG3FA and ICG4FA exhibited improved photophysical properties in biological media, high receptor affinity, and selective uptake in FRαpositive cells, while maintaining compatibility with existing clinical imaging systems. Collectively, these platforms establish complementary strategies for FGS to improve tumor contrast, specificity, and clinical applicability for real-time surgical guidance
- Notes:
- Source: Dissertations Abstracts International, Volume: 87-12, Section: B.
- Advisors: Delikatny, Edward James Committee members: Marmorstein, Ronen; Singhal, Sunil; Tsourkas, Andrew; Trauner, Dirk
- Ph.D. University of Pennsylvania 2026
- Vendor supplied data
- Local Notes:
- School code: 0175
- ISBN:
- 9798247973768
- Access Restriction:
- Restricted for use by site license
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