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Implementation of oxygen enhanced magnetic resonance imaging (OE-MRI) and a pilot genomic study of hypoxia in bladder cancer xenografts
Shabbir, Rekaya Telfer, B. A. Dickie, B. Reardon, M. Babur, M. Williams, K. West, C. M. L. Choudhury, Ananya Smith, Tim A D
Shabbir, Rekaya
Telfer, B. A.
Dickie, B.
Reardon, M.
Babur, M.
Williams, K.
West, C. M. L.
Choudhury, Ananya
Smith, Tim A D
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Abstract
BACKGROUND/AIM: Patients with hypoxic bladder cancer benefit from hypoxia modification added to radiotherapy, but no biomarkers exist to identify patients with hypoxic tumours. We, herein, aimed to implement oxygen-enhanced MRI (OE-MRI) in xenografts derived from muscle-invasive bladder cancer (MIBC) for future hypoxia biomarker discovery work; and generate gene expression data for future biomarker discovery. MATERIALS AND METHODS: The flanks of female CD-1 nude mice inoculated with HT1376 MIBC cells. Mice with small (300 mm(3)) or large (700 mm(3)) tumours were imaged, breathing air then 100% O(2), 1 h post injection with pimonidazole in an Agilant 7T 16cm bore magnet interfaced to a Bruker Avance III console with a T2-TurboRARE sequence using a dynamic MPRAGE acquisition. Dynamic Spoiled Gradient Recalled Echo images were acquired for 5 min, with 0.1mmol/kg Gd-DOTA (Dotarem, Guerbet, UK) injected after 60 s (1 ml/min). Voxel size and field of view of dynamic contrast enhanced (DCE)-MRI and OE-MRI scans were matched. The voxels considered as perfused with significant post-contrast enhancement (p<0.05) in DCE-MRI scans and tissue were further split into pOxyE (normoxic) and pOxyR (hypoxic) regions. Tumours harvested in liquid N(2), sectioned, RNA was extracted and transcriptomes analysed using Clariom S microarrays. RESULTS: Imaged hypoxic regions were greater in the larger versus smaller tumour. Expression of known hypoxia-inducible genes and a 24 gene bladder cancer hypoxia score were higher in pimonidazole-high versus -low regions: CA9 (p=0.012) and SLC2A1 (p=0.012) demonstrating expected transcriptomic behaviour. CONCLUSION: OE-MRI was successfully implemented in MIBC-derived xenografts. Transcriptomic data derived from hypoxic and non-hypoxic xenograft regions will be useful for future studies.
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Date
2024
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Article
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Shabbir R, Telfer BA, Dickie B, Reardon M, Babur M, Williams K, et al. Implementation of Oxygen Enhanced Magnetic Resonance Imaging (OE-MRI) and a Pilot Genomic Study of Hypoxia in Bladder Cancer Xenografts. Cancer genomics & proteomics. 2024 Jul-Aug;21(4):380-7.