Chemical Synthesis of a Lysyl Oxidase-Based Probe for Positron Emission Tomography Imaging of Tumors
Session Number
Project ID: CHEM 04
Advisor(s)
Dr. Satish Chitneni, University of Chicago
Dr. Atchimnaidu Siriki, University of Chicago
Discipline
Chemistry
Start Date
17-4-2024 9:20 AM
End Date
17-4-2024 9:35 AM
Abstract
The Lysyl oxidase family of enzymes (LOXF) plays a critical role in tumor progression by promoting extracellular matrix remodeling, epithelial-mesenchymal transition, and angiogenesis. Upregulation of LOXF, particularly lysyl oxidase (LOX) and lysyl oxidase-like 2 (LOXL2), is observed in hypoxic tumor microenvironments and is associated with increased invasiveness and metastasis. In this study, we report the chemical synthesis of a probe, termed "LOXi," for non-invasive imaging of LOXL2 expression in tumors using positron emission tomography (PET). The compound is designed to selectively bind to the active site of the LOXL2 enzyme in tumors. We hypothesize that radiolabeling the compound with a positron-emitting radioisotope, such as carbon-11 (11C, half-life = 20 min) or fluorine-18 (18F, half-life = 110 min), will enable PET imaging of LOXL2 expression levels in cancers in living subjects non-invasively, thereby providing a valuable tool for monitoring tumor progression and response to LOXF- targeted therapies. Further development of radiolabeled derivatives of LOXi could enable clinical translation for imaging and therapeutic targeting of LOXF in cancer patients.
Chemical Synthesis of a Lysyl Oxidase-Based Probe for Positron Emission Tomography Imaging of Tumors
The Lysyl oxidase family of enzymes (LOXF) plays a critical role in tumor progression by promoting extracellular matrix remodeling, epithelial-mesenchymal transition, and angiogenesis. Upregulation of LOXF, particularly lysyl oxidase (LOX) and lysyl oxidase-like 2 (LOXL2), is observed in hypoxic tumor microenvironments and is associated with increased invasiveness and metastasis. In this study, we report the chemical synthesis of a probe, termed "LOXi," for non-invasive imaging of LOXL2 expression in tumors using positron emission tomography (PET). The compound is designed to selectively bind to the active site of the LOXL2 enzyme in tumors. We hypothesize that radiolabeling the compound with a positron-emitting radioisotope, such as carbon-11 (11C, half-life = 20 min) or fluorine-18 (18F, half-life = 110 min), will enable PET imaging of LOXL2 expression levels in cancers in living subjects non-invasively, thereby providing a valuable tool for monitoring tumor progression and response to LOXF- targeted therapies. Further development of radiolabeled derivatives of LOXi could enable clinical translation for imaging and therapeutic targeting of LOXF in cancer patients.