Differentiation between Treatment-Induced Necrosis and Recurrent Tumors in Patients with Metastatic Brain Tumors: Comparison among 11C-Methionine-PET,FDG-PET,MR Permeability Imaging,and MRI-ADC—Preliminary Results

BACKGROUND AND PURPOSE:In patients with metastatic brain tumors after gamma knife radiosurgery, the superiority of PET using ¹¹C-methionine for differentiating radiation necrosis and recurrent tumors has been accepted. To evaluate the feasibility of MR permeability imaging, it was compared with PET using ¹¹C-methionine, FDG-PET, and DWI for differentiating radiation necrosis from recurrent tumors.MATERIALS AND METHODS:The study analyzed 18 lesions from 15 patients with metastatic brain tumors who underwent gamma knife radiosurgery. Ten lesions were identified as recurrent tumors by an operation. In MR permeability imaging, the transfer constant between intra- and extravascular extracellular spaces (/minute), extravascular extracellular space, the transfer constant from the extravascular extracellular space to plasma (/minute), the initial area under the signal intensity–time curve, contrast-enhancement ratio, bolus arrival time (seconds), maximum slope of increase (millimole/second), and fractional plasma volume were calculated. ADC was also acquired. On both PET using ¹¹C-methionine and FDG-PET, the ratio of the maximum standard uptake value of the lesion divided by the maximum standard uptake value of the symmetric site in the contralateral cerebral hemisphere was measured (¹¹C-methionine ratio and FDG ratio, respectively). The receiver operating characteristic curve was used for analysis.RESULTS:The area under the receiver operating characteristic curve for differentiating radiation necrosis from recurrent tumors was the best for the ¹¹C-methionine ratio (0.90) followed by the contrast-enhancement ratio (0.81), maximum slope of increase (millimole/second) (0.80), the initial area under the signal intensity–time curve (0.78), fractional plasma volume (0.76), bolus arrival time (seconds) (0.76), the transfer constant between intra- and extravascular extracellular spaces (/minute) (0.74), extravascular extracellular space (0.68), minimum ADC (0.60), the transfer constant from the extravascular extracellular space to plasma (/minute) (0.55), and the FDG-ratio (0.53). A significant difference in the ¹¹C-methionine ratio (P < .01), contrast-enhancement ratio (P < .01), maximum slope of increase (millimole/second) (P < .05), and the initial area under the signal intensity–time curve (P < .05) was evident between radiation necrosis and recurrent tumor.CONCLUSIONS:The present study suggests that PET using ¹¹C-methionine may be superior to MR permeability imaging, ADC, and FDG-PET for differentiating radiation necrosis from recurrent tumors after gamma knife radiosurgery for metastatic brain tumors.

Stereotactic radiosurgery such as gamma knife radiosurgery (GK) and CyberKnife (Accuray, Sunnyvale, California) is an effective method for treating intracranial neoplasms.^1,2 For metastatic tumors of the brain, stereotactic radiosurgery has generally been the main tool used in therapeutic regimens.^3,4 Although stereotactic radiosurgery is an effective treatment method, it has a risk of radiation necrosis. Radiation necrosis after stereotactic radiosurgery for metastatic tumors of the brain is more common than previously reported.^5,6 It generally occurs 3–12 months after therapy⁷ and often resembles recurrent tumors on conventional imaging techniques, such as MR imaging,^8–11 CT,¹² and SPECT.¹³ Differentiating radiation necrosis and recurrent tumor is extremely important because of the different treatment implications. Histologic examination from a biopsy or resection may aid in differentiating these 2 events. However, a noninvasive method is needed for diagnosing whether a contrast-enhanced lesion with surrounding edema on conventional MR imaging is radiation necrosis or a recurrent tumor.Advanced MR imaging techniques including MR spectroscopy,¹⁴ DWI,¹⁵ and DTI¹⁶ have been used for differentiation of radiation necrosis and recurrent tumors. The CTP technique has also been reported as promising in this field.¹⁷ CTP has the advantage of using widely available CT scanners, though x-ray exposure and administration of ionizing contrast material limit the clinical use. In radionuclide studies, SPECT with ²⁰¹TI-chloride,¹⁸ technetium Tc99m-sestamibi,^{19 123}I-alfa-methyl-L-tyrosine,²⁰O-(2-¹⁸F]-fluoroethyl)-L-tyrosine (FET-PET),^21,22 6-¹⁸F]-fluoro-L-dopa (FDOPA),²³ and FDG-PET^24–26 have been reported to differentiate between radiation necrosis and recurrent tumors. Compared with those studies, the superiority of PET with ¹¹C-methionine (MET) for differentiating radiation necrosis and recurrent tumors has been accepted because of the high sensitivity and specificity.^27–31 However, MET-PET is not widely available. Dynamic contrast-enhanced MR imaging with a contrast agent has been used to characterize brain tumors^32,33 and stroke.³⁴MR permeability imaging with dynamic contrast-enhanced–MR imaging based on the Tofts model³⁵ has recently been developed and used for evaluating cerebrovascular diseases,³⁶ brain tumors,^37–39 nasopharyngeal carcinomas,^40,41 rectal carcinomas,⁴² and prostate carcinomas.⁴³ The endothelial permeability of vessels in brain tumors can be quantitatively acquired with MR permeability imaging. The vascular microenvironment in tumors can be measured by parameters such as influx transfer constant, reverse transfer constant, and the extravascular extracellular space.⁴⁴ These parameters may reflect tissue characteristics including vascular density, a damaged blood-brain barrier, vascularity, and neoangiogenesis.⁴⁴ If the feasibility of MR permeability imaging for differentiating radiation necrosis and recurrent tumors could be demonstrated, this technique may contribute to the management of patients after stereotactic radiosurgery and conventional radiation therapy because MR permeability imaging is widely available. To evaluate the feasibility of MR permeability imaging in the present study, we compared it with MET-PET, FDG-PET, and DWI for differentiating radiation necrosis from recurrent tumor after GK in patients with metastatic brain tumors.