Histomolecular Validation of [18F]-FACBC in Gliomas Using Image-Localized Biopsies

Abstract

Background: Gliomas have a heterogeneous nature, and identifying the most aggressive parts of the tumor and defining tumor borders are important for histomolecular diagnosis, surgical resection, and radiation therapy planning. This study evaluated [¹⁸F]-FACBC PET for glioma tissue classification.

Methods: Pre-surgical [¹⁸F]-FACBC PET/MR images were used during surgery and image-localized biopsy sampling in patients with high- and low-grade glioma. TBR was compared to histomolecular results to determine optimal threshold values, sensitivity, specificity, and AUC values for the classification of tumor tissue. Additionally, PET volumes were determined in patients with glioblastoma based on the optimal threshold. [¹⁸F]-FACBC PET volumes and diagnostic accuracy were compared to ce-T1 MRI. In total, 48 biopsies from 17 patients were analyzed.

Results: [¹⁸F]-FACBC had low uptake in non-glioblastoma tumors, but overall higher sensitivity and specificity for the classification of tumor tissue (0.63 and 0.57) than ce-T1 MRI (0.24 and 0.43). Additionally, [¹⁸F]-FACBC TBR was an excellent classifier for IDH1-wildtype tumor tissue (AUC: 0.83, 95% CI: 0.71-0.96). In glioblastoma patients, PET tumor volumes were on average eight times larger than ce-T1 MRI volumes and included 87.5% of tumor-positive biopsies compared to 31.5% for ce-T1 MRI.

Conclusion: The addition of [¹⁸F]-FACBC PET to conventional MRI could improve tumor classification and volume delineation.

Keywords: MRI; [18F]-FACBC; amino acid PET; glioma.

Figure 1

Patient inclusion flowchart.

Figure 2

Flowchart of the inclusion process and classification of samples based on IHC analysis only (purple arrows), combined IHC and/or DNA methylation analysis (green arrows), and DNA methylation analysis only (blue arrows). IHC, immunohistochemical; LGG, low-grade glioma; HGG, high-grade glioma.

Figure 3

[¹⁸F]-FACBC TBRs for biopsies designated as (A) non-tumor tissue, low-grade and high-grade, and (B) astrocytoma, oligodendroglioma, and glioblastoma, as determined by IHC analysis and/or DNA methylation analysis. TBR was significantly higher for HGG than non-HGG (p = 0.037). LGG, low-grade glioma; HGG, high-grade glioma; TBR, tumor-to-background ratio.

Figure 4

[¹⁸F]-FACBC TBR for biopsies designated as (A) IDH1-mutated or -wildtype, (B) ATRX-lost or -retained, and (C) low- or increased-cell-density, as determined by IHC analysis and/or DNA methylation analysis. There was a significant difference in TBR for all three properties (IDH1 status: p < 0.001, ATRX status: p < 0.01, cell density: p = 0.049). TBR, tumor-to-background ratio.

Figure 5

ROC plots of TBR value as predictor for (A) tumor tissue (HGG/LGG vs. non-tumor tissue), (B) high-grade glioma (HGG vs. LGG/non-tumor tissue), (C) IDH1-wildtype tumor (IDH1wt tumor tissue vs. IDH1-mutated tumor tissue/non-tumor tissue), or (D) ATRX-retained tumor (ATRX-retained tumor tissue vs. ATRX-lost tumor tissue/non-tumor tissue).

Figure 6

FLAIR (green), PET (red), and ce-T1 (cyan) MRI volumes for 3 glioblastoma patients ((A) female, 52; (B) male, 46; (C) female, 50) shown on FLAIR MRI, ce-T1 MRI, and PET/FLAIR images. Blue circles show biopsy coordinates classified as HGG (A,B), while the pink circle shows biopsy coordinates classified as non-tumor tissue (C). Two HGG biopsies from (A) and one from (B) did not show contrast enhancement, but were positive for [¹⁸F]-FACBC PET at a threshold of TBR = 2. One non-tumor biopsy from C was ce-T1 positive, but did not have [¹⁸F]-FACBC uptake.