Molecular imaging of gliomas with PET: opportunities and limitations

Abstract

Neuroimaging enables the noninvasive evaluation of glioma and is considered to be one of the key factors for individualized therapy and patient management, since accurate diagnosis and demarcation of viable tumor tissue is required for treatment planning as well as assessment of treatment response. Conventional imaging techniques like MRI and CT reveal morphological information but are of limited value for the assessment of more specific and reproducible information about biology and activity of the tumor. Molecular imaging with PET is increasingly implemented in neuro-oncology, since it provides additional metabolic information of the tumor, both for patient management as well as for evaluation of newly developed therapeutics. Different molecular processes have been proposed to be useful, like glucose consumption, expression of amino acid transporters, proliferation rate, membrane biosynthesis, and hypoxia. Thus, PET might help neuro-oncologists gain further insights into tumor biology by "true molecular imaging" as well as understand treatment-related phenomena. This review describes the method of PET acquisition as well as the tracers used to image biological processes in gliomas. Furthermore, it considers the clinical impact of PET on the use of currently available radiotracers, which were shown to be potentially valuable for discrimination between neoplastic and nonneoplastic tissue, as well as on tumor grading, determinination of treatment response, and providing an outlook toward further developments.

Fig. 1.

Transversal [¹⁸F]FET PET, fused PET MR, and contrast-enhanced T1-weighted MR images are shown. Similar increased tracer uptake was found in a patient with oligoastrocytoma WHO II (OA) (upper row) and glioblastoma (GBM) (lower row) that did not allow the differentiation between low- and high-grade glioma. However, additional assessment of tracer kinetics enabled the right diagnosis, by showing increasing activity in the low-grade glioma and an early peak followed by a decrease in the high-grade glioma.

Fig. 2.

Transversal MR, fused PET MR, and [¹⁸F]FET PET images are shown. Upper row: diffuse T2-hyperintensity in the left insula with focal and moderate [¹⁸F]FET uptake in a patient with astrocytoma WHO II. Middle row: MRI shows a diffuse T2-hyperintensity, without contrast enhancement in T1-weighted MR images (not shown), and [¹⁸F]FET PET demonstrates significant tracer uptake in a patient with histologically proven anaplastic astrocytoma WHO III. Lower row: a patient with glioblastoma without contrast enhancement in T1-weighted MR but markedly increased [¹⁸F]FET uptake.

Fig. 3.

Combined [¹⁸F]FET PET MR clearly demarcate the anaplastic focus in a patient with heterogeneous glioma. Slightly increased contrast enhancement but highly increased tracer uptake proved this to be an anaplastic oligoastrocytoma WHO III (A), whereas nonenhancing tumor parts without significant tracer uptake were shown to constitute an astrocytoma WHO II (B).

Fig. 4.

Tumor delineation and target volume definition for treatment planning substantially differs, depending on the image modality used. Highest tumor volume is suggested on T2-weighted MRI. [¹⁸F]FET uptake considerably exceeds the contrast enhancement in T1-weighted MRI.

Fig. 5.

Postradiogenic contrast enhancement on MRI coupled with pathologically increased tracer uptake on PET were highly suggestive for glioblastoma progression, which was confirmed by means of histology (upper row), whereas contrast enhancement on MRI with only slightly increased and homogeneous [¹⁸F]FET uptake (lower row) was shown to be treatment associated by follow-up examinations.