Graduation Date
Summer 8-9-2024
Document Type
Thesis
Degree Name
Master of Science (MS)
Programs
Pharmaceutical Sciences
First Advisor
Jered Garrison
Abstract
Targeted radionuclide therapy (TRT) has emerged as a promising cancer treatment by offering precise delivery of radioisotopes to cancer cells via molecular targets. Recent advancements in the small molecule TRTs offer efficient targeting and rapid clearance, reducing off-target toxicity. The Neurotensin receptor 1 (NTSR1) targeted small molecule antagonist 3BP-227 when labeled with [177Lu], has demonstrated effective tumor targeting but suffers from rapid washout from the target cancer cell, limiting its therapeutic potential.
To enhance tumor retention and therapeutic efficacy of the NTSR1-targeted TRT, the Garrison laboratory has developed a novel approach utilizing cysteine cathepsins (CCs) and the E64 inhibitor to form a cysteine cathepsin trapping agent (CCTA). This method involves forming high molecular weight adducts upon internalization, with significantly increasing tumor retention and the deliverable therapeutic dose.
This project aims to synthesize an activity-based probe (ABP) with biotin and fluorophore, fluorescein Isothiocyanate (FITC) tags conjugated to the CCTA-NTSR1 pharmacophore, and the E64 antagonist analogue. This ABP will subsequently facilitate the isolation and quantification of high molecular weight adducts formed after internalization and the identification of the adduct-binding proteins. Additionally, the fluorophore FITC tag will further allow real-time visualization in vitro to enhance our understanding of adduct-forming biology.
Recommended Citation
Khairnar, Aadarsh, "Synthesis and characterization of an activity-based probe to isolate and quantify adduct formation in NTSR1 TRT." (2024). Theses & Dissertations. 860.
https://digitalcommons.unmc.edu/etd/860
Comments
Copyright 2024, the authors