Dynamic O-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography differentiates brain metastasis recurrence from radiation injury after radiotherapy

Abstract

Background: The aim of this study was to investigate the potential of dynamic O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) PET for differentiating local recurrent brain metastasis from radiation injury after radiotherapy since contrast-enhanced MRI often remains inconclusive.

Methods: Sixty-two patients (mean age, 55 ± 11 y) with single or multiple contrast-enhancing brain lesions (n = 76) on MRI after radiotherapy of brain metastases (predominantly stereotactic radiosurgery) were investigated with dynamic 18F-FET PET. Maximum and mean tumor-to-brain ratios (TBRmax, TBRmean) of 18F-FET uptake were determined (20-40 min postinjection) as well as tracer uptake kinetics (ie, time-to-peak and slope of time-activity curves). Diagnoses were confirmed histologically (34%; 26 lesions in 25 patients) or by clinical follow-up (66%; 50 lesions in 37 patients). Diagnostic accuracies of PET parameters for the correct identification of recurrent brain metastasis were evaluated by receiver-operating-characteristic analyses or the chi-square test.

Results: TBRs were significantly higher in recurrent metastases (n = 36) than in radiation injuries (n = 40) (TBRmax 3.3 ± 1.0 vs 2.2 ± 0.4, P < .001; TBRmean 2.2 ± 0.4 vs 1.7 ± 0.3, P < .001). The highest accuracy (88%) for diagnosing local recurrent metastasis could be obtained with TBRs in combination with the slope of time-activity curves (P < .001).

Conclusions: The results of this study confirm previous preliminary observations that the combined evaluation of the TBRs of 18F-FET uptake and the slope of time-activity curves can differentiate local brain metastasis recurrence from radiation-induced changes with high accuracy. 18F-FET PET may thus contribute significantly to the management of patients with brain metastases.

Keywords: FET PET; kinetic analysis; radiation-induced changes; radionecrosis; stereotactic radiosurgery.

Fig. 1.

58-year old patient (#4) with a brain metastasis of a non–small cell lung cancer. Twenty-nine months after stereotactic radiosurgery (SRS), MRI suggests tumor recurrence. In line with MRI findings, ¹⁸F-FET PET shows increased metabolic activity (TBR_mean = 2.2), and the slope of the late phase of the TAC (20–50 min postinjection) is −0.72 SUV/h. Histology after resection was consistent with a recurrent brain metastasis (hematoxylin and eosin stain; original magnification ×400; scale bar, 1000 µm).

Fig. 2.

61-year old patient (#52) with a brain metastasis of a non–small cell lung cancer. Nine months after stereotactic radiosurgery (SRS), MRI suggests tumor recurrence. In contrast, ¹⁸F-FET PET shows no increased metabolic activity (TBR_mean = 1.6), and the slope of the TAC is 0.38 SUV/h. Histology after stereotactic biopsy revealed fibrohyaline-thickened blood vessel walls and amorphic tissue necroses with rims of macrophages. The findings are compatible with actinic angiopathy and radiation necrosis (hematoxylin and eosin stain; original magnification ×100; scale bar, 1000 µm).