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. 2025 Jan;52(2):669-682.
doi: 10.1007/s00259-024-06935-z. Epub 2024 Oct 4.

Pre-operative dual-time-point [18F]FET PET differentiates CDKN2A/B loss and PIK3CA mutation status in adult-type diffuse glioma: a single-center prospective study

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Pre-operative dual-time-point [18F]FET PET differentiates CDKN2A/B loss and PIK3CA mutation status in adult-type diffuse glioma: a single-center prospective study

Dong Yun Lee et al. Eur J Nucl Med Mol Imaging. 2025 Jan.

Abstract

Purpose: While [18F]FET PET plays a complementary role in glioma imaging, it needs to be more comprehensively understood for improved characterization of glioma prior to surgery given the evolving landscape of molecular neuropathology. Thus, we investigated the utility of pre-operative dual-time-point [18F]FET PET in correlation with next-generation sequencing (NGS) data in patients with adult-type diffuse glioma (ADG).

Methods: Adult patients who were suspected to have primary glioma were prospectively recruited between June 2021 and January 2024. They underwent pre-operative dual-time-point static PET/CT at 20 min (early) and 80 min (delay) after [18F]FET injection. Semi-quantitative parameters of the hottest lesion (SUVmax) of tumour and the hottest lesion-to-normal brain ratio (TBRmax) were assessed from each summed image. Furthermore, the percentage changes (△) of SUVmax and TBRmax between two images were calculated. Histopathology of glioma was determined according to the 2021 WHO classification and NGS data.

Results: This study investigated a dozen genes in 76 patients, of whom 51 had isocitrate dehydrogenase (IDH)-wild-type glioblastoma, 13 had IDH-mutant astrocytoma, and 12 had IDH-mutant oligodendroglioma. Every tumour was [18F]FET-avid having TBRmax more than 1.6. Patients with CDKN2A/B loss had significantly higher values of SUVmax (5.7 ± 1.6 vs. 4.7 ± 1.3, p = 0.004; 5.0 ± 1.4 vs. 4.4 ± 1.2, p = 0.026) and TBRmax (6.5 ± 1.8 vs. 5.1 ± 1.7, p = 0.001; 5.3 ± 1.5 vs. 4.3 ± 1.3, p = 0.004) in both scans than patients without CDKN2A/B loss, even after adjustment for age, MRI enhancement, tumor grade and type of pathology. Furthermore, patients with PIK3CA mutation (16.2 ± 11.8 vs. 6.7 ± 11.6, p = 0.007) had significantly higher △SUVmax than patients without PIK3CA mutation, even after adjustment for age, MRI enhancement, tumor grade, and type of pathology.

Conclusion: Among the dozen genes investigated in this prospective study in patients with ADG, we found out that CDKN2A/B loss and PIK3CA mutation status could be differentiated by pre-operative dual-time-point [18F]FET PET/CT.

Keywords: Adult-type diffuse glioma; CDKN2A/B loss; Dual-time-point [18F]FET PET; NGS data; PIK3CA mutation.

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Conflict of interest statement

Declarations. Competing interests: None. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Review Board of our institution (approval no. 2021 − 0520). Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent to publish: The authors affirm that human research participants provided informed consent for publication of the images in Fig. 5 and Supplementary Fig. 1.

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