Towards standardization of 18F-FET PET imaging: do we need a consistent method of background activity assessment?

Abstract

BackgroundPET with O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) has reached increasing clinical significance for patients with brain neoplasms. For quantification of standard PET-derived parameters such as the tumor-to-background ratio, the background activity is assessed using a region of interest (ROI) or volume of interest (VOI) in unaffected brain tissue. However, there is no standardized approach regarding the assessment of the background reference. Therefore, we evaluated the intra- and inter-reader variability of commonly applied approaches for clinical 18F-FET PET reading.The background activity of 20 18F-FET PET scans was independently evaluated by 6 readers using a (i) simple 2D-ROI, (ii) spherical VOI with 3.0 cm diameter, and (iii) VOI consisting of crescent-shaped ROIs; each in the contralateral, non-affected hemisphere including white and gray matter in line with the European Association of Nuclear Medicine (EANM) and German guidelines. To assess intra-reader variability, each scan was evaluated 10 times by each reader. The coefficient of variation (CoV) was assessed for determination of intra- and inter-reader variability. In a second step, the best method was refined by instructions for a guided background activity assessment and validated by 10 further scans.ResultsCompared to the other approaches, the crescent-shaped VOIs revealed most stable results with the lowest intra-reader variabilities (median CoV 1.52%, spherical VOI 4.20%, 2D-ROI 3.69%; p < 0.001) and inter-reader variabilities (median CoV 2.14%, spherical VOI 4.02%, 2D-ROI 3.83%; p = 0.001). Using the guided background assessment, both intra-reader variabilities (median CoV 1.10%) and inter-reader variabilities (median CoV 1.19%) could be reduced even more.ConclusionsThe commonly applied methods for background activity assessment show different variability which might hamper 18F-FET PET quantification and comparability in multicenter settings. The proposed background activity assessment using a (guided) crescent-shaped VOI allows minimization of both intra- and inter-reader variability and might facilitate comprehensive methodological standardization of amino acid PET which is of interest in the light of the anticipated EANM technical guidelines.

Evaluation of factors influencing 18F-FET uptake in the brain

“…Out of a series of patients with suspicious brain lesions who were admitted for 18 F-FET PET to the Institute of Neuroscience and Medicine in Jülich (Germany) from February 2010 to April 2017, 107 scans which revealed no abnormality in 18 F-FET PET and which had been rated in the medical reports as “negative scans” with respect to tumour diagnosis, were retrospectively identified by two experienced nuclear physicians (AV and GS). Negative scans were defined as showing 18 F-FET uptake in the suspected lesion area (identified by corresponding MR images) to be indistinguishable from that of the normal brain within a TBR max range of 0.9–1.1, which is in line with the expectable background SUV changes (± 8%) in the brain for this radiopharmaceutical ( Unterrainer et al, 2017 ). Other inclusion criteria for further data evaluation were age > 18 years, no pre-treatment with radio- or chemotherapy or received therapy with dexamethasone, and complete coverage of the brain by the PET acquisition which was essential for data analysis.…”

“…In the majority of studies, however, tracer uptake in the tumour was quantified by the ratio of SUV max or SUV mean in the tumour to the SUV mean in a background region in the contralateral hemisphere expressed as maximal and mean tumour-to-brain ratios (TBR max and TBR mean ) ( Jansen et al, 2012 , Jansen et al, 2015 , Mehrkens et al, 2008 , Misch et al, 2015 , Pauleit et al, 2005 , Pöpperl et al, 2007 , Rapp et al, 2013 , Stockhammer et al, 2008 ). This method is based on the assumption that 18 F-FET uptake in the normal brain is relatively homogeneous although there is some discussion about the optimal positioning of the region of interest in the normal brain ( Unterrainer et al, 2017 ). Nevertheless, it cannot be excluded that physiological variations of SUV mean of 18 F-FET uptake in background could influence TBRs and the results of semi-quantitative analysis.…”

Voxel-wise analysis of dynamic 18F-FET PET: a novel approach for non-invasive glioma characterisation

“…summation images [ 15 , 27 ]. Background (BG) values were derived from a crescent-shaped volume of interest (VOI) as described previously [ 28 ]. VOIs were defined within the PMOD View tool (version 3.5, PMOD Technologies, Zurich, Switzerland).…”

Imaging glioma biology: spatial comparison of amino acid PET, amide proton transfer, and perfusion-weighted MRI in newly diagnosed gliomas

“…Standardized uptake values (SUV) were calculated from patient weight and injected activity. For background correction, a circular ROI was placed in gray and white matter of the non-tumor-bearing hemisphere by IV and BW [22].…”