Accurate Differentiation of Recurrent Gliomas from Radiation Injury by Kinetic Analysis of α-¹¹C-Methyl-l-Tryptophan PET

Abstract

PET of amino acid transport and metabolism may be more accurate than conventional neuroimaging in differentiating recurrent gliomas from radiation-induced tissue changes. α-11C-methyl-l-tryptophan (11C-AMT) is an amino acid PET tracer that is not incorporated into proteins but accumulates in gliomas, mainly because of tumoral transport and metabolism via the immunomodulatory kynurenine pathway. The aim of this study was to evaluate the usefulness of 11C-AMT PET supplemented by tracer kinetic analysis for distinguishing recurrent gliomas from radiation injury. Methods Twenty-two 11C-AMT PET scans were obtained in adult patients who presented with a lesion suggestive of tumor recurrence on conventional MRI 1–6 y (mean, 3 y) after resection and postsurgical radiation of a World Health Organization grade II–IV glioma. Lesional standardized uptake values were calculated, as well as lesion-to-contralateral cortex ratios and 2 kinetic 11C-AMT PET parameters (volume of distribution [VD], characterizing tracer transport, and unidirectional uptake rate [K]). Tumor was differentiated from radiation-injured tissue by histopathology (n = 13) or 1-y clinical and MRI follow-up (n = 9). Accuracy of tumor detection by PET variables was assessed by receiver-operating-characteristic analysis. Results All 11C-AMT PET parameters were higher in tumors (n = 12) than in radiation injury (n = 10) (P ≤ 0.012 in all comparisons). The lesion-to-cortex K-ratio most accurately identified tumor recurrence, with highly significant differences both in the whole group (P < 0.0001) and in lesions with histologic verification (P = 0.006); the area under the receiver-operating-characteristic curve was 0.99. A lesion-to-cortex K-ratio threshold of 1.39 (i.e., a 39% increase) correctly differentiated tumors from radiation injury in all but 1 case (100% sensitivity and 91% specificity). In tumors that were high-grade initially (n = 15), a higher lesion-to-cortex K-ratio threshold completely separated recurrent tumors (all K-ratios ≥ 1.70) from radiation injury (all K-ratios < 1.50) (100% sensitivity and specificity). Conclusion Kinetic analysis of dynamic 11C-AMT PET images may accurately differentiate between recurrent World Health Organization grade II–IV infiltrating gliomas and radiation injury. Separation of unidirectional uptake rates from transport can enhance the differentiating accuracy of 11C-AMT PET. Applying the same approach to other amino acid PET tracers might also improve their ability to differentiate recurrent gliomas from radiation injury.

Assessment of Tryptophan Uptake and Kinetics Using 1-(2-18F-Fluoroethyl)-l-Tryptophan and α-11C-Methyl-l-Tryptophan PET Imaging in Mice Implanted with Patient-Derived Brain Tumor Xenografts

“…Nevertheless, the high 18 F-FETrp uptake in the bladder and pancreas suggests that this tracer would not allow visualization of tumors in these organs because of high background activity. Despite the differences in distribution, both tracers demonstrated similarly low and continuous brain accumulation, suggesting that 18 F-FETrp will be suitable for the imaging of intracranial brain tumors as previously established with 11 C-AMT (18)(19)(20)(21)(22)(23)(24)(25)(26).…”

“…These studies demonstrated variably high 11 C-AMT uptake in gliomas (18,23,24) and meningiomas (21) and showed strong prognostic value for survival in patients with recurrent glioblastoma (20). Furthermore, 11 C-AMT uptake characteristics distinguished recurrent gliomas from radiation injury (25) and glioblastoma from metastatic brain tumors (26), allowing tryptophan PET imaging as a possible clinical diagnostic tool. The development of a tryptophan analog with a longer half-life isotope such as 18 F would permit widespread clinical application of tryptophan PET imaging.…”

In vivo metabolism of tryptophan in meningiomas is mediated by indoleamine 2,3-dioxygenase 1

“…Preoperative AMT-PET studies were performed in 10 patients with meningioma (6 grade I, 2 grade II and 1 grade III) using a Siemens EXACT/ HR whole-body positron emission tomograph (Siemens Medical Systems) as described previously. 7,23 Briefly, after 6 h of fasting, AMT (37 MBq/kg) was administered intravenously. Twentyfive minutes after tracer injection, a dynamic emission scan of anti-mouse HRP (Southern Biotech).…”

Amino acid PET in neuro-oncology: applications in the clinic

“…11 C]methyl-L-tryptophan [6,7,19]. It could be demonstrated that this observation may be especially helpful for prognostication, which is of great importance for patient counseling.…”