2023 World Conference on Lung Cancer (Posters)-P1.13. Proof-of-mechanism for a Diagnostic Probe Generating D5-Ethanol Asan On-Breath Reporter Molecule for Lung Cancer - Evolution Phase 1.

P1.13. Proof-of-mechanism for a Diagnostic Probe Generating D5-Ethanol Asan On-Breath Reporter Molecule for Lung Cancer - Evolution Phase 1. - PDF(Abstract)

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This document discusses a study conducted to evaluate the potential use of volatile metabolites in breath as a diagnostic modality for lung cancer. The study aims to optimize the signal-to-noise ratio in breath, which is a complex matrix, by administering a probe compound specific to tumour-associated extracellular β-glucuronidase. The compound, D5-ethyl-βD-glucuronide, releases D5-ethanol as a unique volatile reporter when hydrolyzed by β-glucuronidase. <br /><br />The study uses two approaches to establish proof of mechanism. Firstly, lung tissue samples from primary tumors, lymph node metastases, and normal lung tissue were immunostained to evaluate the presence of β-glucuronidase. Elevated levels of extracellular β-glucuronidase were observed in the majority of stage 1, 2, and 3 non-small cell lung cancers. In adjacent non-malignant tissue in lung cancer subjects and non-malignant lung tissue in controls, staining was limited to intracellular sources. <br /><br />Secondly, a phase 1 trial was conducted, where D5-ethyl-βD-glucuronide was administered to 43 individuals. The probe was found to be safe, and the cleavage product, D5-ethanol, could be detected in a subset of participants' breath. The levels of D5-ethanol were related to the volume of breath collected. <br /><br />Overall, this study demonstrates proof of mechanism for the cleavage of the volatile reporter molecule, D5-ethanol, from D5-ethyl-βD-glucuronide in humans. This approach has the potential to optimize the signal-to-noise ratio of a breath test and could be used as an innovative breath-based test for early detection of lung cancer. The promising results from this study provide a foundation for a phase 2 dose-finding study to further explore the diagnostic performance of this breath test approach.

Asset Subtitle

Marc Schee

Meta Tag

Speaker Marc Schee

Topic Screening & Early Detection: Biomarkers/Imaging Technology

Keywords

volatile metabolites

breath

diagnostic modality

lung cancer

signal-to-noise ratio

probe compound

tumour-associated extracellular β-glucuronidase

D5-ethyl-βD-glucuronide

D5-ethanol

proof of mechanism