[18F]-fluoro-ethyl-L-tyrosine PET: a valuable diagnostic tool in neuro-oncology, but not all that glitters is glioma

Abstract

Background: To assess the sensitivity and specificity of [(18)F]-fluoro-ethyl-l-tyrosine ((18)F-FET) PET in brain tumors and various non-neoplastic neurologic diseases.

Methods: We retrospectively evaluated (18)F-FET PET scans from 393 patients grouped into 6 disease categories according to histology (n = 299) or distinct MRI findings (n = 94) (low-grade/high-grade glial/nonglial brain tumors, inflammatory lesions, and other lesions). (18)F-FET PET was visually assessed as positive or negative. Maximum lesion-to-brain ratios (LBRs) were calculated and compared with MRI contrast enhancement (CE), which was graded visually on a 3-point scale (no/moderate/intense).

Results: Sensitivity and specificity for the detection of brain tumor were 87% and 68%, respectively. Significant differences in LBRs were detected between high-grade brain tumors (LBR, 2.04 ± 0.72) and low-grade brain tumors (LBR, 1.52 ± 0.70; P < .001), as well as among inflammatory (LBR, 1.66 ± 0.33; P = .056) and other brain lesions (LBR, 1.10 ± 0.37; P < .001). Gliomas (n = 236) showed (18)F-FET uptake in 80% of World Health Organization (WHO) grade I, 79% of grade II, 92% of grade III, and 100% of grade IV tumors. Low-grade oligodendrogliomas, WHO grade II, had significantly higher (18)F-FET uptakes than astrocytomas grades II and III (P = .018 and P = .015, respectively). (18)F-FET uptake showed a strong association with CE on MRI (P < .001) and was also positive in 52% of 157 nonglial brain tumors and nonneoplastic brain lesions.

Conclusions: (18)F-FET PET has a high sensitivity for the detection of high-grade brain tumors. Its specificity, however, is limited by passive tracer influx through a disrupted blood-brain barrier and (18)F-FET uptake in nonneoplastic brain lesions. Gliomas show specific tracer uptake in the absence of CE on MRI, which most likely reflects biologically active tumor.

Figures

Fig. 1.

Statistical analysis of LBR and CE on MRI T1w. (A) 18F-FET uptake quantification (ie, LBR) according to histological subgroups and WHO grading. Significant differences in LBRs were detected between high-grade (HG) brain tumors (median LBR, 2.04 ± 0.72) and low-grade (LG) brain tumors (median LBR, 1.52 ± 0.70; P < .001), as well as among inflammatory brain lesions (median LBR, 1.66 ± 0.33; P = .056) and other brain lesions (median LBR, 1.10 ± 0.37; P < .001; ANOVA Bonferroni post-hoc analysis). (B) There was no LBR difference when stratifying the brain tumors to glial and nonglial histologies of HG glial (median LBR, 1.99 ± 0.74) vs HG nonglial tumor (median LBR, 2.09 ± 0.62) and LG glial (median LBR, 1.54 ± 0.69) vs LG nonglial tumor (median LBR, 1.38 ± 0.73). No significant differences were observed between HG gliomas and HG nonglial tumors or between LG gliomas and LG nonglial tumors. (C) Oligodendroglioma (ODG) WHO grade II (median LBR, 2.21 ± 0.88) showed significantly higher LBR than astrocytoma [A] grade II (n = 41, median LBR, 1.36 ± 0.19, P = .018) or anaplastic astrocytoma [AA] grade III (n = 10, median LBR, 1.55 ± 0.52, P = .015, ANOVA Bonferroni post-hoc analysis). No statistical difference was seen between glioblastoma (GBM) grade IV (median LBR, 1.86 ± 0.57) and oligoastrocytoma (OAZ) grade II (median LBR, 1.16 ± 0.16, P = .091) or between ODG II and A II. An ODG grade III (n = 1) showed the highest uptake of all brain lesions (LBR, 3.33). (D) Association between LBR and CE intensity on MRI (no CE, n = 157, median LBR = 1.42 ± 0.55; moderate CE, n = 77, median LBR = 1.88 ± 0.74; intense CE, n = 139, median LBR = 2.2 ± 0.67; P< .001, ANOVA Bonferroni post-hoc analysis). (E) CE intensity on MRI stratified to the 6 histological brain lesion subtypes. HG and LG brain tumors as well as inflammatory lesions showed positive tracer uptake despite absence of CE. In the “other” group, 18F-FET signal intensity is directly associated with CE on MRI. *LBR calculation: only patients from the Innsbruck patient cohort (n = 373) were considered; PA, pilocytic astrocytoma, astrocytoma, oligodendroglioma; OA, oligoastrocytoma; AA, anaplastic astrocytoma; AOA, anaplastic oligoastrocytoma; AO, anaplastic oligodendroglioma; GBM, glioblastoma.

Fig. 2.

18F-FET uptake in subacute ischemic and active inflammatory brain lesions. (A) Patient with a subacute ischemic infarction after a venous sinus thrombosis with CE on MRI T1w due to enhanced BBB permeability within the infarct area. The BBB disruption causes unspecific tracer uptake by passive non-carrier-mediated influx into the brain parenchyma. (B) A patient with multiple sclerosis presented with a subcortical active inflammatory brain lesion with central CE. Patients with active neuroinflammatory brain lesions, (C) primary CNS vasculitis, (D) mastoiditis of the right ear with secondary bacterial meningoencephalitis. Both active inflammatory brain lesions showed an intensive focal 18F-FET uptake independently of CE on MRI T1w.