Current Landscape and Emerging Fields of PET Imaging in Patients with Brain Tumors

Abstract

The number of positron-emission tomography (PET) tracers used to evaluate patients with brain tumors has increased substantially over the last years. For the management of patients with brain tumors, the most important indications are the delineation of tumor extent (e.g., for planning of resection or radiotherapy), the assessment of treatment response to systemic treatment options such as alkylating chemotherapy, and the differentiation of treatment-related changes (e.g., pseudoprogression or radiation necrosis) from tumor progression. Furthermore, newer PET imaging approaches aim to address the need for noninvasive assessment of tumoral immune cell infiltration and response to immunotherapies (e.g., T-cell imaging). This review summarizes the clinical value of the landscape of tracers that have been used in recent years for the above-mentioned indications and also provides an overview of promising newer tracers for this group of patients.

Keywords: FACBC; FDOPA; FET; amino acid; brain metastases; glioma; immunoPET; molecular imaging.

Figure 1

Chemical structure of radiolabeled amino acids.

Figure 2

Radiation necrosis and chronic inflammation in a patient with brain metastases of a B-Raf proto-oncogene (BRAF)-mutated malignant melanoma who had been treated with whole-brain radiation therapy combined with concurrent dabrafenib plus trametinib. Twenty-four months later, the contrast-enhanced magnetic resonance imaging (MRI) indicates a recurrence of the brain metastases (left panel), whereas the O-(2-[¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET) positron-emission tomography (PET) shows only insignificant metabolic activity and is consistent with the findings of treatment-related MRI changes. Neuropathological findings (right panel) after stereotactic biopsy show signs of radiation necrosis as well as considerable T-cell infiltration. (A) Hyaline, eosinophilic necrosis with evidence of a necrotic vessel wall (arrowhead). (B) Vital brain parenchyma besides necrosis with activated microglia cells (arrowhead), and blood vessels with lymphocyte infiltrates (arrows) without evidence of tumor cells (inserted box). (C) Adjacent to inflamed blood vessels (arrows), a resorption of necroses by macrophages (block arrows) as well as activated microglia cells (arrowheads) and astrocytes in the brain parenchyma (inserted box). (D) The main population of intra- and perivascular T-cell infiltrates are CD3⁺ (arrow), but also CD4⁺ (inserted box left) and CD8⁺ (inserted box right) T-cells contribute to the infiltrates (modified from Galldiks et al. [10], with permission from Oxford University Press).

Figure 3

[⁶⁴Cu]-DOTA-trastuzumab positron-emission tomography (PET) and contrast-enhanced magnetic resonance imaging (MRI) performed one day after initiation of treatment with trastuzumab in a patient with a human epidermal growth factor receptor 2 (HER2)-positive breast cancer with brain metastases. In single brain metastases, [⁶⁴Cu]-DOTA-trastuzumab PET helps to improve lesion detection (arrow) (modified from Tamura et al. [160], with permission from the Society of Nuclear Medicine and Molecular Imaging).

Figure 4

Detection of immune response in a patient with recurrent glioblastoma using 2-chloro-2′-deoxy-2′-[¹⁸F]fluoro-9-b-D-arabinofuranosyl-adenine ([¹⁸F]CFA) positron-emission tomography (PET) and advanced magnetic resonance imaging (MRI) before (upper panel) and after treatment with dendritic cell vaccination and programmed cell death receptor-1 (PD-1) blockade using pembrolizumab (lower panel). Following treatment, [¹⁸F]CFA uptake is considerably increased, indicating an immune-cell infiltration, and helps distinguishing tumor progression from inflammation (modified from Antonios et al. [169], with permission from the National Academy of Sciences).