Quantitative parametric maps of O-(2-[18F]fluoroethyl)-L-tyrosine kinetics in diffuse glioma.
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ABSTRACT:
SUBMITTER: Koopman T
PROVIDER: S-EPMC7074601 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThis 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.ResultsThe 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 VT as calculated by the plasma input model (r?=?0.97). The 60-90 min standardized uptake value (SUV) showed better correlation with VT (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 VT and CBF in the tumour regions (r?=?0.61, p?=?0.007).ConclusionUptake 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 VT. VT shows correlation with CBF in tumour.
| S-EPMC6068050 | biostudies-literature
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.
| S-EPMC6938530 | biostudies-literature
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.
| S-EPMC9319157 | biostudies-literature
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.
| S-EPMC11282134 | biostudies-literature
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.
| S-EPMC5554515 | biostudies-literature
Project description:[18F]Flortaucipir is a PET tau tracer used to visualize tau binding in Alzheimer's disease (AD) in vivo. The present study evaluated the performance of several methods to obtain parametric images of [18F]flortaucipir. One hundred and thirty minutes dynamic PET scans were performed in 10 AD patients and 10 controls. Parametric images were generated using different linearization and basis function approaches. Regional binding potential (BPND) and volume of distribution (VT) values obtained from the parametric images were compared with corresponding values derived using the reversible two-tissue compartment model (2T4k_VB). Performance of SUVr parametric images was assessed by comparing values with distribution volume ratio (DVR) and SRTM-derived BPND estimates obtained using non-linear regression (NLR). Spectral analysis (SA) (r2 = 0.92; slope = 0.99) derived VT correlated well with NLR-derived VT. RPM (r2 = 0.95; slope = 0.98) derived BPND correlated well with NLR-derived DVR. Although SUVr80-100 min correlated well with NLR-derived DVR (r2 = 0.91; slope = 1.09), bias in SUVr appeared to depend on uptake time and underlying level of specific binding. In conclusion, RPM and SA provide parametric images comparable to the NLR estimates. Individual SUVr values are biased compared with DVR and this bias requires further study in a larger dataset in order to understand its consequences.
| S-EPMC7044757 | biostudies-literature
Project description:PURPOSE: Intracavitary radioimmunotherapy (RIT) offers an effective adjuvant therapeutic approach in patients with malignant gliomas. Since differentiation between recurrence and reactive changes following RIT has a critical impact on patient management, the aim of this study was to analyse the value of serial O-(2-[(18)F]fluoroethyl)-L: -tyrosine (FET) PET scans in monitoring the effects of this locoregional treatment. METHODS: Following conventional therapy, 24 glioma patients (5 WHO III, 19 WHO IV) underwent one to five RIT cycles with either (131)I-labelled (n=19) or (188)Re-labelled (n=5) anti-tenascin antibodies. Patients were monitored with serial FET PET scans (2-12 scans). For semiquantitative evaluation, maximal tumoural uptake (TU(max)) was evaluated and the ratio to background (BG) was calculated. Results of PET were correlated with histopathological findings (n=9) and long-term clinical follow-up for up to 87 months. RESULTS: In seven tumour-free patients, PET revealed slightly increasing but homogeneous FET uptake surrounding the resection cavity with a peak up to 18 months following RIT (TU(max)/BG 2.07+/-0.25) but stable or decreasing values during further follow-up (last follow-up: TU(max)/BG 1.63+/-0.22). Seventeen patients developed regrowth of residual tumour/tumour recurrence showing additional nodular FET uptake (TU(max)/BG 2.79+/-0.53). A threshold value of 2.4 (TU(max)/BG) allowed best differentiation between recurrence and reactive changes (sensitivity 82%, specificity 100%). CONCLUSION: FET PET is a sensitive tool for monitoring the effects of locoregional RIT. Homogeneous, slightly increasing FET uptake around the tumour cavity with a peak up to 18 months after RIT, followed by stable or decreasing uptake, points to benign, therapy-related changes. In contrast, nodular uptake is a reliable indicator of recurrence.
| S-EPMC1998889 | biostudies-other
Project description:Introduction: [11C]Metomidate ([11C]MTO), the methyl ester analogue of etomidate, was developed as a positron emission tomography (PET) radiotracer for adrenocortical tumours and has also been suggested for imaging in primary aldosteronism (PA). A disadvantage of [11C]MTO is the rather high non-specific binding in the liver, which impacts both visualization and quantification of the uptake in the right adrenal gland. Furthermore, the short 20-minute half-life of carbon-11 is a logistic challenge in the clinical setting. Objectives: The aim of this study was to further evaluate the previously published fluorine-18 (T1/2=109.5 min) etomidate analogue, para-chloro-2-[18F]fluoroethyl etomidate; [18F]CETO, as an adrenal PET tracer. Methods: In vitro experiments included autoradiography on human and cynomolgus monkey (non-human primate, NHP) tissues and binding studies on adrenal tissue from NHPs. In vivo studies with [18F]CETO in mice, rats and NHP, using PET and CT/MRI, assessed biodistribution and binding specificity in comparison to [11C]MTO. Results: The binding of [18F]CETO in the normal adrenal cortex, as well as in human adrenocortical adenomas and adrenocortical carcinomas, was shown to be specific, both in vitro (in humans) and in vivo (in rats and NHP) with an in vitro Kd of 0.66 nM. Non-specific uptake of [18F]CETO in NHP liver was found to be low compared to that of [11C]MTO. Conclusions: High specificity of [18F]CETO to the adrenal cortex was demonstrated, with in vivo binding properties qualitatively surpassing those of [11C]MTO. Non-specific binding to the liver was significantly lower than that of [11C]MTO. [18F]CETO is a promising new PET tracer for imaging of adrenocortical disease and should be evaluated further in humans.
| S-EPMC8040415 | biostudies-literature
Project description:Oxime antidotes regenerate organophosphate-inhibited acetylcholinesterase (AChE). Although they share a common mechanism of AChE reactivation, the rate and amount of oxime that enters the brain are critical to the efficacy, a process linked to the oxime structure and charge. Using a platform based on the organophosphate [18 F]-VXS as a positron emission tomography tracer for active AChE, the in vivo distribution of [18 F]-VXS was evaluated after an LD50 dose (250 μg/kg) of the organophosphate paraoxon (POX) and following oximes as antidotes. Rats given [18 F]-VXS tracer alone had significantly higher radioactivity (two- to threefold) in the heart and lung than rats given LD50 POX at 20 or 60 min prior to [18 F]-VXS. When rats were given LD50 POX followed by 2-PAM (cationic), RS194b (ionizable), or monoisonitrosoacetone (MINA) (neutral), central nervous system (CNS) radioactivity returned to levels at or above untreated naive rats (no POX), whereas CNS radioactivity did not increase in rats given the dication oximes HI-6 or MMB-4. MINA showed a significant, pairwise increase in CNS brain radioactivity compared with POX-treated rats. This new in vivo dynamic platform using [18 F]-VXS tracer measures and quantifies peripheral and CNS relative changes in AChE availability after POX exposure and is suitable for comparing oxime delivery and AChE reactivation in rats.
| S-EPMC7677195 | biostudies-literature
Project description:BackgroundSubventricular zone (SVZ) involvement is associated with a dismal prognosis in patients with glioblastoma multiforme (GBM). Dual-time point (dtp) O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET/CT (PET) may be a time- and cost-effective alternative to dynamic FET PET, but its prognostic value, particularly with respect to SVZ involvement, is unknown.MethodsThirty-five patients had two scans 5-15 and 50-60 min after i.v. FET injection to define tumor volumes and SVZ involvement before starting radiotherapy. Associations between clinical progression markers, MRI- and dtp FET PET-based tumor volumes, or SVZ involvement and progression-free (PFS) and overall survival (OS) were assessed in univariable and multivariable analyses.ResultsThe extent of resection was not related to outcomes. Albeit non-significant, dtp FET PET detected more SVZ infiltration than MRI (60% vs. 51%, p = 0.25) and was significantly associated with poor survival (p < 0.03), but PET-T1-Gad volumes were larger in this group (p < 0.002). Survival was shorter in patients with larger MRI tumor volumes, larger PET tumor volumes, and worse Karnofsky performance status (KPS), with fused PET-T1-Gad and KPS significant in multivariable analysis (p < 0.03). Uptake kinetics was not associated with treatment outcomes.ConclusionsFET PET-based tumor volumes may be useful for predicting worse prognosis glioblastoma. Although the presence of SVZ infiltration is linked to higher PET/MRI-based tumor volumes, the independent value of dtp FET PET parameters and SVZ infiltration as prognostic markers pre-irradiation has not been confirmed.
| S-EPMC6398237 | biostudies-literature