Dataset Information

Quantification of O-(2-[¹⁸F]fluoroethyl)-L-tyrosine kinetics in glioma.

ABSTRACT:

Background

This study identified the optimal tracer kinetic model for quantification of dynamic O-(2-[¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET) positron emission tomography (PET) studies in seven patients with diffuse glioma (four glioblastoma, three lower grade glioma). The performance of more simplified approaches was evaluated by comparison with the optimal compartment model. Additionally, the relationship with cerebral blood flow-determined by [¹⁵O]H₂O PET-was investigated.

Results

The optimal tracer kinetic model was the reversible two-tissue compartment model. Agreement analysis of binding potential estimates derived from reference tissue input models with the distribution volume ratio (DVR)-1 derived from the plasma input model showed no significant average difference and limits of agreement of -?0.39 and 0.37. Given the range of DVR-1 (-?0.25 to 1.5), these limits are wide. For the simplified methods, the 60-90 min tumour-to-blood ratio to parent plasma concentration yielded the highest correlation with volume of distribution V_T as calculated by the plasma input model (r?=?0.97). The 60-90 min standardized uptake value (SUV) showed better correlation with V_T (r?=?0.77) than SUV based on earlier intervals. The 60-90 min SUV ratio to contralateral healthy brain tissue showed moderate agreement with DVR with no significant average difference and limits of agreement of -?0.24 and 0.30. A significant but low correlation was found between V_T and CBF in the tumour regions (r?=?0.61, p?=?0.007).

Conclusion

Uptake of [¹⁸F]FET was best modelled by a reversible two-tissue compartment model. Reference tissue input models yielded estimates of binding potential which did not correspond well with plasma input-derived DVR-1. In comparison, SUV ratio to contralateral healthy brain tissue showed slightly better performance, if measured at the 60-90 min interval. SUV showed only moderate correlation with V_T. V_T shows correlation with CBF in tumour.

SUBMITTER: Koopman T

PROVIDER: S-EPMC6068050 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Quantification of O-(2-[<sup>18</sup>F]fluoroethyl)-L-tyrosine kinetics in glioma.

Koopman Thomas T Verburg Niels N Schuit Robert C RC Pouwels Petra J W PJW Wesseling Pieter P Windhorst Albert D AD Hoekstra Otto S OS de Witt Hamer Philip C PC Lammertsma Adriaan A AA Boellaard Ronald R Yaqub Maqsood M

EJNMMI research 20180731 1

<h4>Background</h4>This study identified the optimal tracer kinetic model for quantification of dynamic O-(2-[<sup>18</sup>F]fluoroethyl)-L-tyrosine ([<sup>18</sup>F]FET) positron emission tomography (PET) studies in seven patients with diffuse glioma (four glioblastoma, three lower grade glioma). The performance of more simplified approaches was evaluated by comparison with the optimal compartment model. Additionally, the relationship with cerebral blood flow-determined by [<sup>15</sup>O]H<sub ...[more]

PMID: 30066053

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Project description:BackgroundConventional scale production of small batches of PET tracers (e.g. for preclinical imaging) is an inefficient use of resources. Using O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET), we demonstrate that simple microvolume radiosynthesis techniques can improve the efficiency of production by consuming tiny amounts of precursor, and maintaining high molar activity of the tracers even with low starting activity.ProceduresThe synthesis was carried out in microvolume droplets manipulated on a disposable patterned silicon "chip" affixed to a heater. A droplet of [18F]fluoride containing TBAHCO3 was first deposited onto a chip and dried at 100?°C. Subsequently, a droplet containing 60?nmol of precursor was added to the chip and the fluorination reaction was performed at 90?°C for 5?min. Removal of protecting groups was accomplished with a droplet of HCl heated at 90?°C for 3?min. Finally, the crude product was collected in a methanol-water mixture, purified via analytical-scale radio-HPLC and formulated in saline. As a demonstration, using [18F]FET produced on the chip, we prepared aliquots with different molar activities to explore the impact on preclinical PET imaging of tumor-bearing mice.ResultsThe microdroplet synthesis exhibited an overall decay-corrected radiochemical yield of 55?±?7% (n?=?4) after purification and formulation. When automated, the synthesis could be completed in 35?min. Starting with <?370?MBq of activity, ~?150?MBq of [18F]FET could be produced, sufficient for multiple in vivo experiments, with high molar activities (48-119?GBq/?mol). The demonstration imaging study revealed the uptake of [18F]FET in subcutaneous tumors, but no significant differences in tumor uptake as a result of molar activity differences (ranging 0.37-48?GBq/?mol) were observed.ConclusionsA microdroplet synthesis of [18F]FET was developed demonstrating low reagent consumption, high yield, and high molar activity. The approach can be expanded to tracers other than [18F]FET, and adapted to produce higher quantities of the tracer sufficient for clinical PET imaging.

Project description:O-(2-[18F]fluoroethyl)-L-tyrosine (FET) is a widely used amino acid tracer for positron emission tomography (PET) imaging of brain tumours. This retrospective study and survey aimed to analyse our extensive database regarding the development of FET PET investigations, indications, and the referring physicians' rating concerning the role of FET PET in the clinical decision-making process. Between 2006 and 2019, we performed 6534 FET PET scans on 3928 different patients against a backdrop of growing demand for FET PET. In 2019, indications for the use of FET PET were as follows: suspected recurrent glioma (46%), unclear brain lesions (20%), treatment monitoring (19%), and suspected recurrent brain metastasis (13%). The referring physicians were neurosurgeons (60%), neurologists (19%), radiation oncologists (11%), general oncologists (3%), and other physicians (7%). Most patients travelled 50 to 75 km, but 9% travelled more than 200 km. The role of FET PET in decision-making in clinical practice was evaluated by a questionnaire consisting of 30 questions, which was filled out by 23 referring physicians with long experience in FET PET. Fifty to seventy per cent rated FET PET as being important for different aspects of the assessment of newly diagnosed gliomas, including differential diagnosis, delineation of tumour extent for biopsy guidance, and treatment planning such as surgery or radiotherapy, 95% for the diagnosis of recurrent glioma, and 68% for the diagnosis of recurrent brain metastases. Approximately 50% of the referring physicians rated FET PET as necessary for treatment monitoring in patients with glioma or brain metastases. All referring physicians stated that the availability of FET PET is essential and that it should be approved for routine use. Although the present analysis is limited by the fact that only physicians who frequently referred patients for FET PET participated in the survey, the results confirm the high relevance of FET PET in the clinical diagnosis of brain tumours and support the need for its approval for routine use.

Project description:PurposeThere is currently no ideal radiotracer for imaging bacterial infections. Radiolabelled D-amino acids are promising candidates because they are actively incorporated into the peptidoglycan of the bacterial cell wall, a structural feature which is absent in human cells. This work describes fluorine-18 labelled analogues of D-tyrosine and D-methionine, O-(2-[18F]fluoroethyl)-D-tyrosine (D-[18F]FET) and S-(3-[18F]fluoropropyl)-D-homocysteine (D-[18F]FPHCys), and their pilot evaluation studies as potential radiotracers for imaging bacterial infection.ProceduresD-[18F]FET and D-[18F]FPHCys were prepared in classical fluorination-deprotection reactions, and their uptake in Staphylococcus aureus and Pseudomonas aeruginosa was evaluated over 2 h. Heat killed bacteria were used as controls. A clinically-relevant foreign body model of S. aureus infection was established in Balb/c mice, as well as a sterile foreign body to mimic inflammation. The ex vivo biodistribution of D-[18F]FPHCys in the infected and inflamed mice was evaluated after 1 h, by dissection and gamma counting. The uptake was compared to that of [18F]FDG.ResultsIn vitro uptake of both D-[18F]FET and D-[18F]FPHCys was specific to live bacteria. Uptake was higher in S. aureus than in P. aeruginosa for both radiotracers, and of the two, higher for D-[18F]FPHCys than D-[18F]FET. Blocking experiments with non-radioactive D-[19F]FPHCys confirmed specificity of uptake. In vivo, D-[18F]FPHCys had greater accumulation in S. aureus infection compared with sterile inflammation, which was statistically significant. As anticipated, [18F]FDG showed no significant difference in uptake between infection and inflammation.ConclusionsD-[18F]FPHCys uptake was higher in infected tissues than inflammation, and represents a fluorine-18 labelled D-AA with potential to detect a S. aureus reference strain (Xen29) in vivo. Additional studies are needed to evaluate uptake of this radiotracer in clinical isolates.

Project description:Aim: Positron emission tomography (PET) imaging is a useful tool for assisting in correct differentiation of tumor progression from reactive changes, and the radiolabeled amino acid analog tracer O-(2-18F-fluoroethyl)-L-tyrosine (FET)-PET is amongst the most frequently used. The FET-PET images need to be quantitatively correct in order to be used clinically, which require accurate attenuation correction (AC) in PET/MRI. The aim of this study was to evaluate the use of the subject-specific MR-derived AC method RESOLUTE in post-operative brain tumor patients. Methods: We analyzed 51 post-operative brain tumor patients (68 examinations, 200 MBq [18F]-FET) investigated in a PET/MRI scanner. MR-AC maps were acquired using: (1) the Dixon water fat separation sequence, (2) the ultra short echo time (UTE) sequences, (3) calculated using our new RESOLUTE methodology, and (4) a same day low-dose CT used as reference "gold standard." For each subject and each AC method the tumor was delineated by isocontouring tracer uptake above a tumor(T)-to-brain background (B) activity ratio of 1.6. We measured B, tumor mean and maximal activity (TMEAN, TMAX), biological tumor volume (BTV), and calculated the clinical metrics TMEAN/B and TMAX/B. Results: When using RESOLUTE 5/68 studies did not meet our predefined acceptance criteria of TMAX/B difference to CT-AC < ±0.1 or 5%, TMEAN/B < ±0.05 or 5%, and BTV < ±2 mL or 10%. In total, 46/68 studies failed our acceptance criteria using Dixon, and 26/68 using UTE. The 95% limits of agreement for TMAX/B was for RESOLUTE (-3%; 4%), Dixon (-9%; 16%), and UTE (-7%; 10%). The absolute error when measuring BTV was 0.7 ± 1.9 mL (N.S) with RESOLUTE, 5.3 ± 10 mL using Dixon, and 1.7 ± 3.7 mL using UTE. RESOLUTE performed best in the identification of the location of peak activity and in brain tumor follow-up monitoring using clinical FET PET metrics. Conclusions: Overall, we found RESOLUTE to be the AC method that most robustly reproduced the CT-AC clinical metrics per se, during follow-up, and when interpreted into defined clinical use cut-off criteria and into the patient history. RESOLUTE is especially suitable for brain tumor patients, as these often present with distorted anatomy where other methods based on atlas/template information might fail.

Dataset Information

Quantification of O-(2-[¹⁸F]fluoroethyl)-L-tyrosine kinetics in glioma.

Background

Results

Conclusion

Publications

Quantification of O-(2-[<sup>18</sup>F]fluoroethyl)-L-tyrosine kinetics in glioma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Quantification of O-(2-[18F]fluoroethyl)-L-tyrosine kinetics in glioma.

Background

Results

Conclusion

Publications

Quantification of O-(2-[<sup>18</sup>F]fluoroethyl)-L-tyrosine kinetics in glioma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Quantification of O-(2-[¹⁸F]fluoroethyl)-L-tyrosine kinetics in glioma.