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Purpose <p>To assess hypoxia-associated host-tumour vascular adaptations and glycolytic metabolism in the chick chorioallantoic membrane (CAM) glioblastoma model.</p> Procedures <p>U251 GBM cells were conditioned under normoxia (21% O₂) or hypoxia (1% O₂) for 72&#xa0;h before implantation onto the CAM on embryonic day 7 (E7). Imaging was performed on E13 using MRI (control-CAM n = 8, normoxic-tumour n = 7, hypoxic-tumour n = 6) and brightfield microscopy (control-CAM n = 7, normoxic-tumour n = 8, hypoxic-tumour n = 7). Tumours were harvested on E14 for histology and gene expression analyses. In a separate cohort of 25 GBM-CAM&#xa0;tumours grown&#xa0;under normoxic conditioning, the correlation of glucose metabolism was assessed using [<sup>18</sup>F]FDG-PET on E12 followed by lactate MRS on E13 (n = 8). </p> Results <p>Normoxia- and hypoxia-conditioned tumour-bearing CAMs exhibited vascular remodelling and significant upregulation of <i>VEGFA</i> and <i>ADM</i> compared to cultured cells. αSMA staining confirmed vessel infiltration in normoxia-conditioned tumours. CAIX staining revealed a hypoxic core in these tumours while hypoxia-conditioned tumours displayed heterogeneous staining. In both conditions, GLUT1 staining colocalised with CAIX staining, indicating hypoxia-associated glycolysis. <i>GLUT1, PDK1</i> and <i>LDHA</i> expression was elevated in CAM tumours relative to tumour cells <i>in vitro.</i> In the metabolic imaging cohort, most tumours exhibited [<sup>18</sup>F]FDG uptake and lactate signal. However, no statistically significant relationship was observed between the two methods.</p> Conclusions <p>The CAM model provides a versatile platform for investigating GBM vascularisation and metabolism. Hypoxic conditioning amplifies transcriptional and vascular changes to the CAM. Although both [<sup>18</sup>F]FDG uptake and lactate were measurable, no significant correlation between the two was observed, potentially reflecting variability in tumour engraftment, vascular delivery of [<sup>18</sup>F]FDG, and microenvironmental influences on lactate accumulation.</p>

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Imaging vascular characteristics and glycolytic metabolism of glioblastoma in a chick embryo model using 1H MRI and [18F]FDG-PET

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月23日

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  • Elisabeth Non Gash,
  • Jan Schulze,
  • Sarah E. Barnett,
  • Mahon L. Maguire,
  • Michael Batie,
  • Mohesh Moothanchery,
  • Stephen Pickup,
  • Ian Scott,
  • Rasheed Zakaria,
  • Judy M. Coulson,
  • Sonia Rocha,
  • Harish Poptani

摘要

Purpose

To assess hypoxia-associated host-tumour vascular adaptations and glycolytic metabolism in the chick chorioallantoic membrane (CAM) glioblastoma model.

Procedures

U251 GBM cells were conditioned under normoxia (21% O₂) or hypoxia (1% O₂) for 72 h before implantation onto the CAM on embryonic day 7 (E7). Imaging was performed on E13 using MRI (control-CAM n = 8, normoxic-tumour n = 7, hypoxic-tumour n = 6) and brightfield microscopy (control-CAM n = 7, normoxic-tumour n = 8, hypoxic-tumour n = 7). Tumours were harvested on E14 for histology and gene expression analyses. In a separate cohort of 25 GBM-CAM tumours grown under normoxic conditioning, the correlation of glucose metabolism was assessed using [18F]FDG-PET on E12 followed by lactate MRS on E13 (n = 8).

Results

Normoxia- and hypoxia-conditioned tumour-bearing CAMs exhibited vascular remodelling and significant upregulation of VEGFA and ADM compared to cultured cells. αSMA staining confirmed vessel infiltration in normoxia-conditioned tumours. CAIX staining revealed a hypoxic core in these tumours while hypoxia-conditioned tumours displayed heterogeneous staining. In both conditions, GLUT1 staining colocalised with CAIX staining, indicating hypoxia-associated glycolysis. GLUT1, PDK1 and LDHA expression was elevated in CAM tumours relative to tumour cells in vitro. In the metabolic imaging cohort, most tumours exhibited [18F]FDG uptake and lactate signal. However, no statistically significant relationship was observed between the two methods.

Conclusions

The CAM model provides a versatile platform for investigating GBM vascularisation and metabolism. Hypoxic conditioning amplifies transcriptional and vascular changes to the CAM. Although both [18F]FDG uptake and lactate were measurable, no significant correlation between the two was observed, potentially reflecting variability in tumour engraftment, vascular delivery of [18F]FDG, and microenvironmental influences on lactate accumulation.