Dataset Information

[18F] FDOPA standardized uptake values of brain tumors are not exclusively dependent on LAT1 expression.

ABSTRACT: [18F]-FDOPA is a labeled amino acid (AA) analog used for positron emission tomography (PET) which is gaining increasing interest in the evaluation of brain tumors (BT). The AA-transporter LAT1 has been shown to be involved in [18F]-FDOPA uptake. The aim of this study was to determine whether the [18F]-FDOPA uptake was correlated with level of LAT1 expression in BT. Twenty-eight BT (including 19 gliomas and 9 metastases) were investigated by [18F]-FDOPA-PET prior to surgery and by anti-LAT1 immunohistochemistry on surgical specimens. The quantitative [18F]-FDOPA measured parameters were SUVmax, SUVmean and SUVpeak. LAT1 expression was quantified using a score (0 to 400). A significant [18F]-FDOPA uptake was associated with a LAT1 score ? 100 (p = 0.02) but there was no linear correlation between intensity of [18F]-FDOPA uptake and score of LAT1 expression whatever the parameters considered. LAT1 expression alone is not sufficient to explain variation of intensity of [18F]-FDOPA uptake in BT.

SUBMITTER: Dadone-Montaudie B

PROVIDER: S-EPMC5609741 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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[18F] FDOPA standardized uptake values of brain tumors are not exclusively dependent on LAT1 expression.

Dadone-Montaudié Bérengère B Ambrosetti Damien D Dufour Maxime M Darcourt Jacques J Almairac Fabien F Coyne John J Virolle Thierry T Humbert Olivier O Burel-Vandenbos Fanny F

PloS one 20170922 9

[18F]-FDOPA is a labeled amino acid (AA) analog used for positron emission tomography (PET) which is gaining increasing interest in the evaluation of brain tumors (BT). The AA-transporter LAT1 has been shown to be involved in [18F]-FDOPA uptake. The aim of this study was to determine whether the [18F]-FDOPA uptake was correlated with level of LAT1 expression in BT. Twenty-eight BT (including 19 gliomas and 9 metastases) were investigated by [18F]-FDOPA-PET prior to surgery and by anti-LAT1 immun ...[more]

PMID: 28937983

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Project description:In this study, kinetic parameters of the cellular proliferation tracer (18)F-3'-deoxy-3'-fluoro-L-thymidine (FLT) and the amino acid probe 3,4-dihydroxy-6-(18)F-fluoro-L-phenylalanine (FDOPA) were measured before and early after the start of therapy, and were used to predict the overall survival (OS) of patients with recurrent malignant glioma using multiple linear regression (MLR) analysis.High-grade recurrent brain tumors in 21 patients (11 men and 10 women, age range 26 - 76 years) were investigated. Each patient had three dynamic PET studies with each probe: at baseline and after 2 and 6 weeks from the start of treatment. Treatment consisted of biweekly cycles of bevacizumab (an angiogenesis inhibitor) and irinotecan (a chemotherapeutic agent). For each study, about 3.5 mCi of FLT (or FDOPA) was administered intravenously and dynamic PET images were acquired for 1 h (or 35 min for FDOPA). A total of 126 PET scans were analyzed. A three-compartment, two-tissue model was applied to estimate tumor FLT and FDOPA kinetic rate constants using a metabolite- and partial volume-corrected input function. MLR analysis was used to model OS as a function of FLT and FDOPA kinetic parameters for each of the three studies as well as their relative changes between studies. An exhaustive search of MLR models using three or fewer predictor variables was performed to find the best models.Kinetic parameters from FLT were more predictive of OS than those from FDOPA. The three-predictor MLR model derived using information from both probes (adjusted R(2)?=?0.83) fitted the OS data better than that derived using information from FDOPA alone (adjusted R(2)?=?0.41), but was only marginally different from that derived using information from FLT alone (adjusted R(2)?=?0.82). Standardized uptake values (either from FLT alone, FDOPA alone, or both together) gave inferior predictive results (best adjusted R(2)?=?0.25).For recurrent malignant glioma treated with bevacizumab and irinotecan, FLT kinetic parameters obtained early after the start of treatment (absolute values and their associated changes) can provide sufficient information to predict OS with reasonable confidence using MLR. The slight increase in accuracy for predicting OS with a combination of FLT and FDOPA PET information may not warrant the additional acquisition of FDOPA PET for therapy monitoring in patients with recurrent glioma.

Project description:PurposeTumor response assessments on positron emission tomography (PET)/magnetic resonance imaging (MRI) scans require correct quantification of radiotracer uptake in tumors and normal organs. Historically, MRI scans have been enhanced with gadolinium (Gd)-based contrast agents, which are now controversial due to brain deposition. Recently, ferumoxytol nanoparticles have been identified as an alternative to Gd-based contrast agents because they provide strong tissue enhancement on MR images but are not deposited in the brain. However, it is not known if the strong T1- and T2-contrast obtained with iron oxide nanoparticles such as ferumoxytol could affect MR-based attenuation correction of PET data. The purpose of our study was to investigate if ferumoxytol administration prior to a 2-deoxy-2-[18F]fluoro-D-glucose [18F]FDG PET/MR scan would change standardized uptake values (SUV) of normal organs.ProceduresThirty pediatric patients (6-18 years) with malignant tumors underwent [18F]FDG-PET/MR scans (dose 3 MBq/kg). Fifteen patients received an intravenous ferumoxytol injection (5 mg Fe/kg) prior to the [18F]FDG-PET/MR scans (group 1). Fifteen additional age- and sex-matched patients received unenhanced [18F]FDG-PET/MR scans (group 2). For attenuation correction of PET data, we used a Dixon-based gradient echo sequence (TR 4.2 ms, TE 1.1, 2.3 ms, FA 5), which accounted for soft tissue, lung, fat, and background air. We used a mixed linear effects model to compare the tissue MRI enhancement, quantified as the signal-to-noise ratio (SNR), as well as tissue radiotracer signal, quantified as SUVmean and SUVmax, between group 1 and group 2. Alpha was assumed at 0.05.ResultsThe MRI enhancement of the blood and solid extra-cerebral organs, quantified as SNR, was significantly higher on ferumoxytol-enhanced MRI scans compared to unenhanced scans (p < 0.001). However, SUVmean and SUVmax values, corrected based on the patients' body weight or body surface area, were not significantly different between the two groups (p > 0.05).ConclusionFerumoxytol administration prior to a [18F]FDG PET/MR scan did not change standardized uptake values (SUV) of solid extra-cerebral organs. This is important, because it allows injection of ferumoxytol contrast prior to a PET/MRI procedure and, thereby, significantly accelerates image acquisition times.

Dataset Information

[18F] FDOPA standardized uptake values of brain tumors are not exclusively dependent on LAT1 expression.

Publications

[18F] FDOPA standardized uptake values of brain tumors are not exclusively dependent on LAT1 expression.

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