Role of O-(2-¹⁸F-Fluoroethyl)-l-Tyrosine PET for Differentiation of Local Recurrent Brain Metastasis from Radiation Necrosis

Abstract

The aim of this study was to investigate the potential of O-(2-18 F-fluoroethyl)-L-tyrosine ( 18 F-FET) PET for differentiating local recurrent brain metastasis from radiation necrosis after radiation therapy because the use of contrast-enhanced MRI for this issue is often difficult. Methods: Thirty-one patients (mean age 6 SD, 53 6 11 y) with single or multiple contrastenhancing brain lesions (n 5 40) on MRI after radiation therapy of brain metastases were investigated with dynamic 18 F-FET PET. Maximum and mean tumor-to-brain ratios (TBR max and TBR mean , respectively; 20-40 min after injection) of 18 F-FET uptake were determined. Time-activity curves were generated, and the time to peak (TTP) was calculated. Furthermore, time-activity curves of each lesion were assigned to one of the following curve patterns: (I) constantly increasing 18 F-FET uptake, (II) 18 F-FET uptake peaking early (TTP # 20 min) followed by a plateau, and (III) 18 F-FET uptake peaking early (TTP # 20 min) followed by a constant descent. The diagnostic accuracy of the TBR max and TBR mean of 18 F-FET uptake and the curve patterns for the correct identification of recurrent brain metastasis were evaluated by receiver-operating-characteristic analyses or Fisher exact test for 2 · 2 contingency tables using subsequent histologic analysis (11 lesions in 11 patients) or clinical course and MRI findings (29 lesions in 20 patients) as reference. Results: Both TBR max and TBR mean were significantly higher in patients with recurrent metastasis (n 5 19) than in patients with radiation necrosis (n 5 21) (TBR max , 3.2 6 0.9 vs. 2.3 6 0.5, P , 0.001; TBR mean , 2.1 6 0.4 vs. 1.8 6 0.2, P , 0.001). The diagnostic accuracy of 18 F-FET PET for the correct identification of recurrent brain metastases reached 78% using TBR max (area under the ROC curve [AUC], 0.822 6 0.07; sensitivity, 79%; specificity, 76%; cutoff, 2.55; P 5 0.001), 83% using TBR mean (AUC, 0.851 6 0.07; sensitivity, 74%; specificity, 90%; cutoff, 1.95; P , 0.001), and 92% for curve patterns II and III versus curve pattern I (sensitivity, 84%; specificity, 100%; P , 0.0001). The highest accuracy (93%) to diagnose local recurrent metastasis was obtained when both a TBR mean greater than 1.9 and curve pattern II or III were present (AUC, 0.959 6 0.03; sensitivity, 95%; specificity, 91%; P , 0.001). Conclusion: Our findings suggest that the combined evaluation of the TBR mean of 18 F-FET uptake and the pattern of the timeactivity curve can differentiate local brain metastasis recurrence from radionecrosis with high accuracy. 18 F-FET PET may thus contribute significantly to the management of patients with brain metastases. The improvement in the treatment of solid tumors has led to an increasing number of patients who experience brain metastases during the course of the disease. Stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT) are commonly used to treat brain metastases, and a growing percentage of patients live long enough to experience a local relapse of these me...

Letter to the Editor: “The role of imaging in the management of progressive glioblastoma. A systematic review and evidence-based clinical practice guideline” [J Neurooncol 2014; 118:435–460]

“…The additional use of dynamic FET PET allows a differentiation of high-grade and low-grade recurrences with a sensitivity and specificity of > 90% [5]. Similar results have also been reported for the differentiation of recurrent brain metastases from radiation-induced changes with an accuracy of 93% [6].…”

18F-fluorodopa positron-emission tomography: an emerging imaging modality for patients with brain metastases

“…Ideally, future studies should be prospective and should compare 18 F-FDOPA PET imaging with histological confirmation, particularly in the setting of recurrent brain metastases. The addition of tracer kinetic analysis and time-activity curve patterns of 18 F-FDOPA PET could also significantly improve sensitivity and specificity, such as has been demonstrated with 18 F-fluoroethyl-tyrosine PET [20].…”

Radiologic Patterns of Necrosis After Proton Therapy of Skull Base Tumors

“…For two lesions, the TBRmean and TBRmax values were raised and higher than the cutoff recently suggested for differentiating recurrent brain metastases from radiation necrosis (>1.95 and >2.55, respectively) 13 . Two lesions had an uptake increasing over time (Pattern I), suggestive of radiation necrosis, whereas two lesions had an uptake stable or decreasing (pattern II and III), previously observed for brain metastasis 13 .…”

“…For two lesions, the TBRmean and TBRmax values were raised and higher than the cutoff recently suggested for differentiating recurrent brain metastases from radiation necrosis (>1.95 and >2.55, respectively) 13 . Two lesions had an uptake increasing over time (Pattern I), suggestive of radiation necrosis, whereas two lesions had an uptake stable or decreasing (pattern II and III), previously observed for brain metastasis 13 . However, when using the combination of both TBRmean < 1.95 or pattern I as typical for radiation necrosis three of the four lesions showing a visible uptake had FET-PET features previously described in radiation necrosis 13 .…”

“…The FET-PET evaluation was based on visible uptake (higher than background), on quantitative measures of mean and maximum tumor-to-background (TBRmean and TBRmax) ratio and on the dynamic changes of uptake over time (30 to 40 13 .…”