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Molecular imaging of Cathepsin E-positive tumors in mice using a novel protease-activatable fluorescent probe
Wael R Abd-Elgaliel1, Zobeida Cruz-Monserrate2, Craig D Logsdon2,3
1Department of Radiology, The Methodist Hospital Research Institute, Weill Cornell Medical College, 6565 Fannin Street, B5-009, Houston, TX 77030, USA.
Unlabelled:
The purpose of this study is to demonstrate the ability of imaging Cathepsin E (Cath E) positive tumors in living animals through selective targeting of Cath E proteolytic activity using a sensitive molecular imaging agent.
Methods:
A peptide-based Cath E imaging probe and a control probe were synthesized for this study. Human Cath E-positive cancer cells (MPanc96-E) were implanted subcutaneously in nude mice. Tumor-bearing mice were examined in vivo with near-infrared fluorescence (NIRF) imaging at various time points after intravenous injection of the Cath E sensing imaging probe. Excised organs and tissues of interest were further imaged ex vivo.
Results:
Upon specific Cath E proteolytic activation, the NIRF signal of the imaging probe a was converted from an optically quenched initial state to a highly fluorescent active state. Imaging probe a was able to highlight the Cath E-positive tumors as early as 24 h post injection. Fluorescent signal in tumor was 3-fold higher than background. The confined specificity of imaging probe a to tumor associated Cath E was verified by using control imaging probe b. Both in vivo and ex vivo imaging results confirmed the superior selectivity and sensitivity of imaging probe a in Cath E imaging.
Conclusions:
The small animal studies demonstrated the capability of probe a for imaging Cath E-positive tumors. The developed optical probe could be applied in early diagnostic imaging and guiding subsequent surgical procedure.
Insights
This study developed a novel molecular imaging agent to detect Cathepsin E (Cath E) positive tumors in vivo. The sensitive probe successfully highlighted tumors, showing potential for early cancer diagnosis and surgical guidance.
Area of Science:
- Biomedical imaging
- Molecular imaging
- Protease activity imaging
Background:
- Cathepsin E (Cath E) is implicated in various cancers.
- Accurate imaging of Cath E-positive tumors is crucial for diagnosis and treatment.
- Current imaging methods may lack specificity and sensitivity.
Purpose of the Study:
- To develop and validate a molecular imaging agent for selective targeting and visualization of Cathepsin E (Cath E) proteolytic activity in vivo.
- To demonstrate the capability of this agent for imaging Cath E-positive tumors in a preclinical model.
Main Methods:
- Synthesis of a peptide-based Cath E imaging probe and a control probe.
- In vivo near-infrared fluorescence (NIRF) imaging of tumors in mice after probe injection.
- Ex vivo imaging of excised tissues for confirmation of probe localization and specificity.
Main Results:
- The Cath E-specific imaging probe showed a significant increase in fluorescence upon proteolytic activation by Cath E.
- Cath E-positive tumors were successfully visualized in vivo as early as 24 hours post-injection.
- Tumor-to-background fluorescence ratios were 3-fold higher, and specificity was confirmed using a control probe.
Conclusions:
- The developed optical probe effectively images Cath E-positive tumors in small animal models.
- This technology holds promise for early diagnostic imaging of Cath E-driven cancers.
- The probe could aid in guiding surgical procedures for improved patient outcomes.
