Combined PET imaging of tumor hypoxia and proliferation in Glioblastoma using a single injection of 18F-FMISO and 18F-FLT: Association with sites of subsequent recurrence.

BACKGROUND

Glioblastoma (GBM) is characterized by intra-tumoral heterogeneity, rapid proliferation, hypoxia-driven radio-resistance, and early recurrence. Gadolinium-Enhanced MRI, the standard of care imaging modality for surgical and radiotherapy planning, lacks specificity for viable tumor burden, particularly in non-enhancing regions.

PURPOSE: This pilot study aimed to evaluate whether preoperative dual-tracer PET using a combined dose of 18FMISO (hypoxia) and 18FLT (proliferation) improves tumor delineation and predicts subsequent local recurrence compared with MRI.

METHODS

Seven patients with WHO grade 4 gliomas (5 GBM, 2 IDH-mutant astrocytomas) underwent preoperative dual-[FMISO+FLT] static PET at 180 min post-injection, and MRI. 6/7 patients underwent resection. Tumor volumes were segmented from PET, contrast-enhanced T1 (T1-Gd), and T2-FLAIR. Postoperative resection cavities were delineated, and follow-up MRI every 3 months was used to identify recurrence. PET-defined tumor volumes extending beyond resection were correlated with subsequent recurrence sites.

RESULTS

Thirteen lesions were analyzed; all showed [FMISO+FLT] uptake (mean activity concentration ratio 1.6 with the cerebellar cortex used as reference region). PET-defined tumor volumes (9.2 cc) were slightly larger than T1-Gd (7.9 cc) but smaller than T2-FLAIR (28.8 cc). PET-defined volumes frequently extended beyond MRI-defined contours (mean non-overlap 6.4 cc vs T1-Gd; 1.5 cc vs. T2-FLAIR). Of six patients undergoing resection, four developed local recurrence within 3.3 months. In all cases, recurrence arose within PET-avid regions outside the resection cavity. The other two patients with complete resection of PET-defined volumes showed a relatively prolonged progression-free-survival (PFS) and including one patient with overall survival exceeding 36 months.

CONCLUSIONS

Dual-[FMISO+FLT] PET is feasible, safe, and can allow delineation of biologically viable tumor subregions, in particular within the MRI T2-FLAIR volume. This approach prospectively identified sites of subsequent local recurrence and may improve surgical planning and radiotherapy dose escalation. Larger validation studies are warranted to establish dual-tracer PET as a precision imaging paradigm in GBM.