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

IF 2.5 4区医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Molecular Imaging and Biology Pub Date : 2026-02-23 DOI:10.1007/s11307-026-02084-x

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

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Abstract

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.

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利用1H MRI和[18F]FDG-PET成像鸡胚模型胶质母细胞瘤血管特征和糖溶代谢。

目的：探讨鸡绒毛膜-尿囊膜（CAM）胶质母细胞瘤模型中与缺氧相关的宿主-肿瘤血管适应性和糖酵解代谢。操作步骤：在胚胎第7天（E7）植入CAM前，将U251 GBM细胞置于常氧（21% O₂）或缺氧（1% O₂）条件下72 h。对E13进行MRI（对照- cam n = 8，正氧-肿瘤n = 7，缺氧-肿瘤n = 6）和明场显微镜（对照- cam n = 7，正氧-肿瘤n = 8，缺氧-肿瘤n = 7）成像。在E14上采集肿瘤进行组织学和基因表达分析。在一个单独的队列中，25个在常氧条件下生长的GBM-CAM肿瘤，使用[18F]FDG-PET在E12上评估葡萄糖代谢的相关性，然后在E13上使用乳酸MRS （n = 8）。结果：与培养细胞相比，常氧和缺氧条件下的肿瘤CAMs表现出血管重构和VEGFA和ADM的显著上调。α - sma染色证实常氧条件下肿瘤有血管浸润。CAIX染色在这些肿瘤中显示一个缺氧核心，而缺氧条件下的肿瘤显示异质染色。在这两种情况下，GLUT1染色与CAIX染色共定位，表明缺氧相关的糖酵解。GLUT1、PDK1和LDHA在CAM肿瘤中的表达高于肿瘤细胞。在代谢成像队列中，大多数肿瘤显示[18F]FDG摄取和乳酸信号。然而，两种方法之间没有统计学上的显著关系。结论：CAM模型为研究GBM血管化和代谢提供了一个通用的平台。缺氧条件会放大CAM的转录和血管变化。虽然[18F]FDG摄取和乳酸都是可测量的，但两者之间没有观察到显著的相关性，这可能反映了肿瘤植入、[18F]FDG的血管输送以及微环境对乳酸积累的影响的变异性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Imaging and Biology 医学-核医学

CiteScore

6.90

自引率

3.20%

发文量

审稿时长

3 months

期刊介绍： Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.