Journal Article DZNE-2026-00546

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APTw CEST MRI in therapy-naive IDH-wildtype glioblastoma: insights into tumor heterogeneity and molecular subtypes.

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2026
Springer Science + Business Media B.V Dordrecht [u.a.]

Journal of neuro-oncology 178(1), 9 () [10.1007/s11060-026-05616-1]

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Abstract: Advanced MRI techniques may provide non-invasive insight into the molecular heterogeneity of glioblastoma. Amide proton transfer-weighted (APTw) chemical exchange saturation transfer (CEST) MRI reflects endogenous protein and peptide content, but its clinical and molecular correlates in therapy-naive glioblastoma, IDH-wildtype, remain incompletely understood.This retrospective single-center study included 53 adult patients with therapy-naive glioblastoma, IDH-wildtype, who underwent preoperative APTw MRI. Median time between imaging and tissue sampling was two days. Median and 90th percentile (p90) APTw signal intensities were extracted from contrast-enhancing (T1-CE) tumor regions and FLAIR-hyperintense regions using automated deep learning-based segmentation with manual quality control. Histological and molecular analyses included MGMT promoter methylation, Ki-67 index, and DNA methylation-based subclassification. Associations were assessed using non-parametric tests, multivariable linear regression, and Cox regression analyses.APTw signal intensity was significantly higher in T1-CE tumor regions than in FLAIR-hyperintense regions (p < 0.0001). Within the T1-CE region, higher APTw signal intensity was modestly associated with younger age. Glioblastomas of the mesenchymal methylation subtype demonstrated significantly higher median and p90 APTw signal intensity compared with RTK1 and RTK2 subtypes, independent of MGMT status and Ki-67 index. APTw signal intensity was not independently associated with PFS or OS.APTw CEST MRI reflects molecular heterogeneity in therapy-naive IDH-wildtype glioblastoma, with potentially increased signal intensity in the mesenchymal subtype. These findings support its possible role as a complementary imaging biomarker for non-invasive molecular characterization.

Keyword(s): Humans (MeSH) ; Glioblastoma: genetics (MeSH) ; Glioblastoma: diagnostic imaging (MeSH) ; Glioblastoma: pathology (MeSH) ; Glioblastoma: metabolism (MeSH) ; Glioblastoma: classification (MeSH) ; Female (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Brain Neoplasms: genetics (MeSH) ; Brain Neoplasms: diagnostic imaging (MeSH) ; Brain Neoplasms: pathology (MeSH) ; Brain Neoplasms: metabolism (MeSH) ; Brain Neoplasms: classification (MeSH) ; Magnetic Resonance Imaging: methods (MeSH) ; Retrospective Studies (MeSH) ; Adult (MeSH) ; Aged (MeSH) ; Isocitrate Dehydrogenase: genetics (MeSH) ; DNA Methylation (MeSH) ; DNA Repair Enzymes: genetics (MeSH) ; Tumor Suppressor Proteins: genetics (MeSH) ; DNA Modification Methylases: genetics (MeSH) ; Amide proton transfer-weighted imaging ; Chemical exchange saturation transfer imaging ; DNA methylation ; Glioblastoma ; MRI ; Mesenchymal subtype glioblastoma ; Receptor tyrosine kinase subtype glioblastoma ; Isocitrate Dehydrogenase ; DNA Repair Enzymes ; Tumor Suppressor Proteins ; MGMT protein, human ; DNA Modification Methylases

Classification:

Contributing Institute(s):
  1. Clinical Neuroimaging (AG Radbruch)
Research Program(s):
  1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2026
Database coverage:
Medline ; Creative Commons Attribution CC BY 4.0 ; OpenAccess ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Springer ; Essential Science Indicators ; IF < 5 ; JCR ; NationallizenzNationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2026-05-20, last modified 2026-05-22