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-(11)C-methyl-l-tryptophan ((11)C-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 (11)C-AMT PET supplemented by tracer kinetic analysis for distinguishing recurrent gliomas from radiation injury.

Methods: Twenty-two (11)C-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 (11)C-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 (11)C-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 (11)C-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 (11)C-AMT PET. Applying the same approach to other amino acid PET tracers might also improve their ability to differentiate recurrent gliomas from radiation injury.

FIGURE 1

Coregistered T1-weighted postgadolinium MR (A), ¹⁸F-FDG PET (B), and ¹¹C-AMT PET (C) images of 31-y-old man (patient 1) with surgically resected WHO grade II oligodendroglioma and suspected tumor recurrence. ¹⁸F-FDG PET showed marked glucose hypometabolism in neighboring cortex, whereas ¹¹C-AMT PET demonstrated increased tryptophan uptake in area with mild contrast enhancement (solid arrows) and in more anterior region without contrast enhancement (dashed arrow). K and K lesion-to-cortex ratios of these 2 areas were similar (posterior area: 0.0070 mL/g/min and 1.60, respectively; anterior area: 0.0066 mL/g/min and 1.51, respectively). Repeated surgery demonstrated grade III oligodendroglioma in both areas.

FIGURE 2

Representative T1-weighted postgadolinium MR and coregistered ¹¹C-AMT PET images of patient with histologically verified glioma recurrence (A and C; patient 6) and patient with pure radiation injury, also verified by histology (B and D; patient 20). MR images showed contrast enhancement in both patients: small contrast-enhancing nodule medial to resection cavity in patient 6 (white arrow; A) and extensive contrast enhancement surrounding resection cavity in patient 20 (B). ¹¹C-AMT PET summed images from 30 to 60 min after tracer injection demonstrated markedly increased uptake of ¹¹C-AMT in both patients. However, kinetic analysis of dynamic PET images (E) revealed higher K (increased slope) and VD (higher y intercept) in recurrent glioma than in area of radiation injury. x-axis represents transformed time (blood time) in minutes. C_t = tracer concentration in tissue; C_p = tracer concentration in plasma.