Accurate differentiation of recurrent gliomas from radiation injury by kinetic analysis of α-11C-methyl-L-tryptophan PET.
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).


CONCLUSIONS
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.
PET Center, Children's Hospital of Michigan, Detroit, MI, USA.
Bálint
B
Alkonyi
Geoffrey R
GR
Barger
Sandeep
S
Mittal
Otto
O
Muzik
Diane C
DC
Chugani
Gautam
G
Bahl
Natasha L
NL
Robinette
William J
WJ
Kupsky
Pulak K
PK
Chakraborty
Csaba
C
Juhász
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D019788:Fluorodeoxyglucose F18; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging; D012372:ROC Curve; D011832:Radiation Injuries / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012015:Reference Standards; D015203:Reproducibility of Results; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D019394:Ki-67 Antigen; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C020774:alpha-methyltryptophan; D014364:Tryptophan