Histopathology-verified comparison of FET PET and contrast-enhanced MRI for tumor visualization in glioblastoma.

2049 Background: In glioblastoma, precise visualization is a prerequisite for optimal resection strategies and accurate radiotherapy volume definition. In routine practice, contrast-enhanced MRI (CE-MRI) is most commonly used; however, it can underestimate tumor extent when viable tumor is present without blood–brain barrier disruption and therefore without contrast uptake. The present study examined whether amino acid PET with O-(2-[ 18 F]fluoroethyl)-L-tyrosine (FET) can better visualize the true distribution of tumor tissue and thereby improve preoperative assessment. Methods: In this prospective, biopsy-validated single-center study, in 61 patients with IDH-wildtype glioblastoma (44 newly diagnosed, 17 recurrent) 472 biopsies spatially correlated with preoperative FET PET and CE-MRI were histopathologically evaluated. Diagnostic metrics were calculated and compared between modalities using McNemar and Chi² tests (p = 0.05). Results: Overall, FET PET identified tumor tissue with significantly higher sensitivity than CE-MRI (91.2% vs. 55.7%; p < 0.001). When benchmarked against T2/FLAIR, FET remained more sensitive (85.3%; p = 0.012) while also demonstrating a pronounced gain in specificity (82.5% vs. 33.3%; p < 0.001). Remarkably, there was the high reliability of FET in regions without MRI contrast enhancement: biopsies taken from FET-positive areas without contrast enhancement showed a positive predictive value of 98.3%. Subgroup analyses consistently demonstrated the advantage of FET across clinical and histological strata, including newly diagnosed and recurrent disease (p < 0.001), as well as within cohorts with resection (p < 0.001; specificity p = 0.03) or biopsy (p < 0.001). Importantly, performance advantages were also observed regardless of histological tumor cell density, with FET exceeding CE-MRI in both histological strata (infiltration zone and solid tumor, both p < 0.001). Conclusions: FET PET demonstrated significant diagnostic superiority over CE-MRI for the visualization of glioblastoma tissue. Comparable positive predictive values in contrast-enhancing and non-enhancing regions indicate that FET PET detects tumor reliably, independent of the blood–brain barrier integrity. These findings support the integration of amino acid PET as an important component in target definition for both surgical and radiation planning in glioblastoma.