Dynamic amino-acid PET in neuro-oncology: a prognostic tool becomes essential

Abstract

Amino-acid PET imaging is an efficient complementary tool to MRI for the assessment of gliomas, principally for high-grade gliomas [1] and is now recommended by the Response Assessment in Neuro-Oncology Group (RANO) [2]. 11C-methyl-l-methionine (11C-MET), O-2-18F-fluoroethyl-l-tyrosine (18F-FET) and 3,4-dihydroxy-6-18F-fluorol-phenylalanine (18F-FDopa) are the three main aminoacid radiotracers used in neuro-oncology PET imaging, with most published studies based on 18F-FET [1–3]. Most nuclear medicine centres only analyse static acquisitions of amino-acid PET imaging. These static acquisitions have proven effective for diagnosing gliomas and for defining the extent of tumour involvement and are particularly useful for treatment planning [4–9]. The European guidelines nevertheless introduced dynamic amino-acid PET utility for the assessment of gliomas [3] and numerous publications on dynamic amino-acid PET imaging also report that this approach yields additional information about tumour biology. Although amino-acid PET imaging primarily detects the expression of l-amino-acid transporters (LAT) in gliomas, additional dynamic parameters may reveal characteristics relating to perfusion and therefore identify features of tumour neovascularization [10]. Several studies initially investigated dynamic analyses in gliomas using 18F-FET [11], then 18F-FDopa [12] and even 11C-MET [13], notwithstanding the short radioactive period of the 11C radio-isotope. Dynamic analysis is based on the assumption that aggressive gliomas (i.e. high-grade gliomas and/or IDH-wildtype gliomas) have high tracer uptake within the first few minutes post-injection (washin), followed by a decrease in the uptake curve (wash-out), while less aggressive gliomas (i.e. low-grade gliomas and/ or IDH-mutant gliomas) typically show a slow increase in amino-acid uptake with the highest values observed during later time frames. As initially suggested by Pöpperl et al. [11], the washout observed in high-grade gliomas might be indicative of micro vessel density and LAT expression but also of disruption of the blood–brain barrier. To date, aminoacid PET dynamic analysis studies have contributed to position dynamic analysis as an essential component of glioma prognostic information and as a useful complementary tool to static images. The prognostic information for glioma kinetic amino PET analysis can be obtained from a scan of only 30–40 min [14]. This represents a significant reduction in the acquisition time normally required for dynamic PET, which had previously restricted the wider application of the analysis in clinical practice. Dynamic PET studies predominantly focus on two parameters extracted from the tumour volume of interest, namely, the time-to-peak (TTP), which represents the time from the beginning of the injection to the maximum SUV, and the slope, which is typically a linear regression of the late phase of the time-activity curve (TAC). Most of the prognostic information from molecular parameters, which is included in the WHO 2016 classification of gliomas [15], is derived from dynamic PET parameters. It has become crucial to non-invasively determine glioma molecular parameters, such as IDH mutation status, since they are associated with better patient outcome [15]. Irrespectively of whether dynamic parameters are based on 18F-FET [16, 17] or 18F-FDopa PET imaging [12], they predict the presence of an IDH mutation at the initial diagnosis with accuracies ranging from 72 to 79% [12, 16, 17]. Static parameters were unable to provide IDH mutation status or provided lower performances. In addition, the prognostic value of dynamic parameters persists even when taking This article is part of the Topical Collection on Oncology—Brain