Replay: Being Sensitive: to Specify When Amino Acid Tracers Accumulate in a Brain Lesion

REPLY: We agree with Dr. Pichler that our report on O-(2-¹⁸F-fluoroethyl)-l-tyrosine (¹⁸F-FET) uptake in primary brain lesions is in line with previous studies and we have cited the corresponding literature correctly. There is no need to point out that fact once again. In comparison with previous studies, the prominent features of our study are the larger size of the patient group, histologic confirmation in nearly all cases, and a clear and reproducible technique of ¹⁸F-FET uptake evaluation. Visual evaluations of ¹⁸F-FET PET scans are subjective and may be difficult for inexperienced physicians. Therefore, the guidelines of the European Association of Nuclear Medicine and German Society of Nuclear Medicine for brain tumor imaging using labeled amino acid analogs recommend the use of a threshold value of the lesion-to-brain ratio to distinguish a positive result from nonspecific amino acid uptake (1,2). Our report provides threshold values of ¹⁸F-FET uptake for primary brain lesions that are essential for clinical decision making (3).

We also agree with Dr. Pichler that knowledge of the mechanisms leading to increased ¹⁸F-FET uptake in nonneoplastic brain lesions is important. We have undertaken several experimental studies of ¹⁸F-FET uptake in animal models of cerebral infarctions, abscesses, and hematoma (4–6). Those studies demonstrated that increased ¹⁸F-FET uptake temporarily occurred in areas with reactive astrocytosis but not in macrophage infiltration or activated microglia. In humans, the histologic finding of pronounced reactive astrocytosis was confirmed in different nonneoplastic lesions that exhibited increased ¹⁸F-FET uptake (7,8). Thus, according to the current knowledge, a high incidental uptake of ¹⁸F-FET in benign brain lesions is most likely due to reactive astrocytosis.

Furthermore, in a clinical study we already addressed the problem of nonspecific brain lesions on MR imaging with low ¹⁸F-FET uptake (9). We observed that normal or low ¹⁸F-FET uptake is a strong predictor for a benign course, with the eventual development of a low-grade glioma.

We would like to emphasize that the data on lesion-to-brain ratios of ¹⁸F-FET uptake in different brain lesions at initial diagnosis may be helpful for decision making but that the additional value of ¹⁸F-FET PET lies in defining an optimal site for biopsy and determining the extent of metabolically active tumor for treatment planning.

• © 2013 by the Society of Nuclear Medicine and Molecular Imaging, Inc.