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.

Highlights

  • PET with O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) has reached increasing clinical significance for patients with brain neoplasms

  • The European Association of Nuclear Medicine (EANM) guideline for brain tumor imaging stated “Interpretation of quantitative results is based on the comparison of tumor-to-background uptake ratio,” and the guideline pointed to a potential source of error by “small regional differences in uptake in normal brain, emphasizing the need for careful choice of an appropriate reference region” [14], there is no procedural recommendation regarding the method of background assessment

  • Several different and inconsistent approaches for background assessment are used in the current literature and in the clinical routine: one approach uses a region of interest (ROI) in the contralateral hemisphere including white and gray matter [15, 16], which is in line with the German guideline for amino acid imaging, which stated that a ROI should be placed in unaffected contralateral brain tissue, “e.g., with a diameter of 50 mm” [17]

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Summary

Introduction

PET with O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) has reached increasing clinical significance for patients with brain neoplasms. 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. Several different and inconsistent approaches for background assessment are used in the current literature and in the clinical routine: one approach uses a region of interest (ROI) in the contralateral hemisphere including white and gray matter [15, 16], which is in line with the German guideline for amino acid imaging, which stated that a ROI should be placed in unaffected contralateral brain tissue, “e.g., with a diameter of 50 mm” [17]. First suggestions were made regarding a softwarebased assessment using [11C]-methionine PET previously [21], there is still no standardized and consistent procedure used in the clinical routine

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