Pretreatment delineation of infiltrating glioma volume remains suboptimal with current neuroimaging techniques. Gadolinium-enhanced T1-weighted (T1-Gad) MR images often underestimate the true extent of the tumor, while T2-weighted images preferentially highlight peritumoral edema. Accumulation of α-[11C]methyl-l-tryptophan (AMT) on positron emission tomography(PET) has been shown in gliomas. To determine whether increased uptake on AMT–PET would detect tumor-infiltrated brain tissue outside the contrast-enhancing region and differentiate it from peritumoral vasogenic edema, volumes and spatial concordance of T1-Gad and T2 MRI abnormalities as well as AMT–PET abnormalities were analyzed in 28 patients with newly-diagnosed WHO grade II–IV gliomas. AMT-accumulating grade I meningiomas were used to define an AMT uptake cutoff threshold that detects the tumor but excludes peri-meningioma vasogenic edema. Tumor infiltration in AMT-accumulating areas was studied in stereotacticallyresected specimens from patients with glioblastoma. In the 28 gliomas, mean AMT–PET-defined tumor volumes were greater than the contrast-enhancing volume, but smaller than T2 abnormalities. Volume of AMT-accumulating tissue outside MRI abnormalities increased with higher tumor proliferative index and was the largest in glioblastomas. Tumor infiltration was confirmed by histopathology from AMT-positive regions outside contrast-enhancing glioblastoma mass, while no or minimal tumor cells were found in AMT-negative specimens. These results demonstrate that increased AMT accumulation on PET detects glioma-infiltrated brain tissue extending beyond the contrast-enhanced tumor mass. While tryptophan uptake is low in peritumoral vasogenic edema, AMT–PET can detect tumor-infiltrated brain outside T2-lesions. Thus, AMT–-PET may assist pretreatment delineation of tumor infiltration, particularly in high-grade gliomas.
Differentiating high-grade gliomas from solitary brain metastases is often difficult by conventional MRI; molecular imaging may facilitate such discrimination. We tested the accuracy of alpha[11C]methyl-L-tryptophan (AMT)-PET imaging to differentiate newly-diagnosed glioblastomas from brain metastases. AMT-PET was performed in 36 adults with suspected brain malignancy. Tumoral AMT accumulation was measured by standardized uptake values (SUVs). Tracer kinetic analysis was also performed to separate tumoral net tryptophan transport (by AMT volume of distribution, VD′) from unidirectional uptake rates using dynamic PET and blood input function. Differentiating accuracy of these PET variables was evaluated and compared to conventional MRI. For glioblastoma/metastasis differentiation, tumoral AMT SUV showed the highest accuracy (74%) and the tumor/cortex VD′ ratio had the highest positive predictive value (82%). The combined accuracy of MRI (size of contrast enhancing lesion) and AMT-PET reached up to 93%. For ring-enhancing lesions, tumor/cortex SUV ratios were higher in glioblastomas than in metastatic tumors and could differentiate these two tumor types with >90% accuracy. These results demonstrate that evaluation of tryptophan accumulation by PET can enhance pre-treatment differentiation of glioblastomas and metastatic brain tumors. This approach may be particularly useful in patients with a newly-diagnosed solitary ring-enhancing mass.
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