There is an urgent need for the development of novel positron emission tomography (PET) tracers for glioma imaging. In this study, we developed a novel PET probe ([18F]VUIIS1018A) by targeting translocator protein (TSPO), an imaging biomarker for glioma. The purpose of this preclinical study was to evaluate this novel TSPO probe for glioma imaging.
ProceduresIn this study, we synthesized [19F]VUIIS1018A and the precursor for radiosynthesis of [18F]VUIIS1018A. TSPO binding affinity was confirmed using a radioligand competitive binding assay in C6 glioma cell lysate. Further, dynamic imaging studies were performed in rats using a microPET system. These studies include displacement and blocking studies for ligand reversibility and specificity evaluation, and compartment modeling of PET data for pharmacokinetic parameter measurement using metabolite-corrected arterial input functions and PMOD.
ResultsCompared to previously reported TSPO tracers including [18F]VUIIS1008 and [18F]DPA-714, the novel tracer [18F]VUIIS1018A demonstrated higher binding affinity and BPND. Pretreatment with the cold analog [19F]VUIIS1018A could partially block tumor accumulation of this novel tracer. Further, compartment modeling of this novel tracer also exhibited a greater tumor-to-background ratio, a higher tumor binding potential and a lower brain binding potential when compared with other TSPO probes, such as [18F]DPA-714 and [18F]VUIIS1008.
ConclusionsThese studies illustrate that [18F]VUIIS1018A can serve as a promising TSPO PET tracer for glioma imaging and potentially imaging of other solid tumors.
相似文献The α2-adrenoceptors mediate many effects of norepinephrine and epinephrine, and participate in the regulation of neuronal, endocrine, cardiovascular, vegetative, and metabolic functions. Of the three receptor subtypes, only α2A and α2C are found in the brain in significant amounts. Subtype-selective positron emission tomography (PET) imaging of α2-adrenoceptors has been limited to the α2C subtype. Here, we report the synthesis of 6-[18F]fluoro-marsanidine, a subtype-selective PET tracer candidate for α2A-adrenoceptors, and its preclinical evaluation in rats and mice.
Procedures6-[18F]Fluoro-marsanidine was synthesized using electrophilic F-18 fluorination with [18F]Selectfluor bis(triflate). The tracer was evaluated in Sprague Dawley rats and in α2A-knockout (KO) and wild-type (WT) mice for subtype selectivity. In vivo PET imaging and ex vivo brain autoradiography were performed to determine the tracer distribution in the brain. The specificity of the tracer for the target was determined by pretreatment with the subtype-non-selective α2-agonist medetomidine. The peripheral biodistribution and extent of metabolism of 6-[18F]fluoro-marsanidine were also analyzed.
Results6-[18F]Fluoro-marsanidine was synthesized with [18F]Selectfluor bis(triflate) in a radiochemical yield of 6.4?±?1.7 %. The molar activity was 3.1 to 26.6 GBq/μmol, and the radiochemical purity was >?99 %. In vivo studies in mice revealed lower uptake in the brains of α2A-KO mice compared to WT mice. The results for selectivity were confirmed by ex vivo brain autoradiography. Blocking studies revealed reduced uptake in α2A-adrenoceptor-rich brain regions in pretreated animals, demonstrating the specificity of the tracer. Metabolite analyses revealed very rapid metabolism of 6-[18F]fluoro-marsanidine with blood-brain barrier-permeable metabolites in both rats and mice.
Conclusion6-[18F]Fluoro-marsanidine was synthesized and evaluated as a PET tracer candidate for brain α2A-adrenoceptors. However, rapid metabolism, extensive presence of labeled metabolites in the brain, and high non-specific uptake in mouse and rat brain make 6-[18F]fluoro-marsanidine unsuitable for α2A-adrenoceptor targeting in rodents in vivo.
相似文献Purpose
Translocator protein (TSPO) concentrations are elevated in glioma, suggesting a role for TSPO positron emission tomography (PET) imaging in this setting. In preclinical PET studies, we evaluated a novel, high-affinity TSPO PET ligand, [18F]VUIIS1008, in healthy mice and glioma-bearing rats.Procedures
Dynamic PET data were acquired simultaneously with [18F]VUIIS1008 injection, with binding reversibility and specificity evaluated in vivo by non-radioactive ligand displacement or blocking. Compartmental analysis of PET data was performed using metabolite-corrected arterial input functions. Imaging was validated with histology and immunohistochemistry.Results
[18F]VUIIS1008 exhibited rapid uptake in TSPO-rich organs. PET ligand uptake was displaceable with non-radioactive VUIIS1008 or PBR06 in mice. Tumor accumulation of [18F]VUIIS1008 was blocked by pretreatment with VUIIS1008 in rats. [18F]VUIIS1008 exhibited improved tumor-to-background ratio and higher binding potential in tumors compared to a structurally similar pyrazolopyrimidine TSPO ligand, [18F]DPA-714.Conclusions
The PET ligand [18F]VUIIS1008 exhibits promising characteristics as a tracer for imaging glioma. Further translational studies appear warranted. 相似文献Myocardial uptake can hamper visualization of lung tumors, atherosclerotic plaques, and inflammatory diseases in 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) studies because it leads to spillover in adjacent structures. Several preparatory pre-imaging protocols (including dietary restrictions and drugs) have been proposed to decrease physiological [18F]FDG uptake by the heart, although their effect on tumor glucose metabolism remains largely unknown. The objective of this study was to assess the effects of a ketogenic diet (as an alternative protocol to fasting) on tumor glucose metabolism assessed by [18F]FDG positron emission tomography (PET) in a mouse model of lung cancer.
ProceduresPET scans were performed 60 min after injection of 18.5 MBq of [18F]FDG. PET data were collected for 45 min, and an x-ray computed tomograph (CT) image was acquired after the PET scan. A PET/CT study was obtained for each mouse after fasting and after the ketogenic diet. Quantitative data were obtained from regions of interest in the left ventricular myocardium and lung tumor.
ResultsThree days on a ketogenic diet decreased mean standard uptake value (SUVmean) in the myocardium (SUVmean 0.95?±?0.36) more than one night of fasting (SUVmean 1.64?±?0.93). Tumor uptake did not change under either dietary condition.
ConclusionsThese results show that 3 days on high-fat diets prior to [18F]FDG-PET imaging does not change tumor glucose metabolism compared with one night of fasting, although high-fat diets suppress myocardial [18F]FDG uptake better than fasting.
相似文献6-[18F]fluoro-l-DOPA ([18F]FDOPA), a positron emission tomography (PET) amino-acid tracer of brain decarboxylase activity, is used to assess the brain dopaminergic system. Using a voxel-based semi-quantitative analysis, this study aimed to determine whether a current brain uptake index of [18F]FDOPA, expressed relative to the occipital background level, varies according to age and gender.
ProceduresOne hundred and seventy-seven subjects were retrospectively included. A whole-brain statistical parametric mapping analysis of the [18F]FDOPA uptake index in parametric PET images was performed at a voxel threshold of p?<?0.05 (corrected) and p?<?0.005 (uncorrected, k cluster >?125).
ResultsStriatal uptake indices were influenced by age, negatively for the caudate nucleus and positively for the putamen, as well as by gender, with a lower left putaminal uptake index in women. Extra-striatal uptake indices were influenced by age, negatively for the frontal cortex and brainstem and positively for the occipital cortex and cerebellum, as well as by gender (diffuse increase in women).
ConclusionsThe uptake index of [18F]FDOPA exhibited significant physiological variations according to age and gender and should therefore be considered for PET interpretation.
相似文献Purpose
2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide labeled with [18F]-fluorine ([18F]EF5), a promising tracer for tumor hypoxia, has previously been synthesized in low yields and low specific radioactivity. In pharmacokinetic evaluations, in the presence of non-radioactive EF5, a uniform and low background uptake and high in vivo stability of [18F]EF5 have been demonstrated. Our purpose was to increase the specific radioactivity of [18F]EF5 to enable to study the pharmacokinetics at trace level. 相似文献The high rates of failure in the radiotherapy target volume suggest that patients with stage II or III non-small-cell lung cancer (NSCLC) should receive an increased total dose of radiotherapy. 2-Deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) and [18F]fluoromisonidazole ([18F]FMISO) (hypoxia) uptake on pre-radiotherapy positron emission tomography (PET)/X-ray computed tomography (CT) have been independently reported to identify intratumor subvolumes at higher risk of relapse after radiotherapy. We have compared the [18F]FDG and [18F]FMISO volumes defined by PET/CT in NSCLC patients included in a prospective study.
ProceduresThirty-four patients with non-resectable lung cancer underwent [18F]FDG and [18F]FMISO PET/CT before (pre-RT) and during radiotherapy (around 42 Gy, per-RT). The criteria were to delineate 40 % and 90 % SUVmax thresholds on [18F]FDG PET/CT (metabolic volumes), and SUV >?1.4 on pre-RT [18F]FMISO PET/CT (hypoxic volume). The functional volumes were delineated within the tumor volume as defined on co-registered CTs.
ResultsThe mean pre-RT and per-RT [18F]FDG volumes were not statistically different (30.4 cc vs 22.2; P?=?0.12). The mean pre-RT SUVmax [18F]FDG was higher than per-RT SUVmax (12.7 vs 6.5; P?<?0.0001). The mean [18F]FMISO SUVmax and volumes were 2.7 and 1.37 cc, respectively. Volume-based analysis showed good overlap between [18F]FDG and [18F]FMISO for all methods of segmentation but a poor correlation for Jaccard or Dice Indices (DI). The DI maximum was 0.45 for a threshold at 40 or 50 %.
ConclusionThe correlation between [18F]FDG and [18F]FMISO uptake is low in NSCLC, making it possible to envisage different management strategies as the studies in progress show.
相似文献Poly (ADP-ribose) polymerase (PARP) inhibitors are extensively studied and used as anti-cancer drugs, as single agents or in combination with other therapies. Most radiotracers developed to date have been chosen on the basis of strong PARP1–3 affinity. Herein, we propose to study AZD2461, a PARP inhibitor with lower affinity towards PARP3, and to investigate its potential for PARP targeting in vivo.
MethodsUsing the Cu-mediated 18F-fluorodeboronation of a carefully designed radiolabelling precursor, we accessed the 18F-labelled isotopologue of the PARP inhibitor AZD2461. Cell uptake of [18F]AZD2461 in vitro was assessed in a range of pancreatic cell lines (PSN-1, PANC-1, CFPAC-1 and AsPC-1) to assess PARP expression and in vivo in xenograft-bearing mice. Blocking experiments were performed with both olaparib and AZD2461.
Results[18F]AZD2461 was efficiently radiolabelled via both manual and automated procedures (9 %?±?3 % and 3 %?±?1 % activity yields non-decay corrected). [18F]AZD2461 was taken up in vivo in PARP1-expressing tumours, and the highest uptake was observed for PSN-1 cells (7.34?±?1.16 %ID/g). In vitro blocking experiments showed a lesser ability of olaparib to reduce [18F]AZD2461 binding, indicating a difference in selectivity between olaparib and AZD2461.
ConclusionTaken together, we show the importance of screening the PARP selectivity profile of radiolabelled PARP inhibitors for use as PET imaging agents.
相似文献Tumor 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.
相似文献To assess in healthy volunteers the whole-body distribution and dosimetry of [11C]metoclopramide, a new positron emission tomography (PET) tracer to measure P-glycoprotein activity at the blood-brain barrier.
ProceduresTen healthy volunteers (five women, five men) were intravenously injected with 387?±?49 MBq of [11C]metoclopramide after low dose CT scans and were then imaged by whole-body PET scans from head to upper thigh over approximately 70 min. Ten source organs (brain, thyroid gland, right lung, myocardium, liver, gall bladder, left kidney, red bone marrow, muscle and the contents of the urinary bladder) were manually delineated on whole-body images. Absorbed doses were calculated with QDOSE (ABX-CRO) using the integrated IDAC-Dose 2.1 module.
ResultsThe majority of the administered dose of [11C]metoclopramide was taken up into the liver followed by urinary excretion and, to a smaller extent, biliary excretion of radioactivity. The mean effective dose of [11C]metoclopramide was 1.69?±?0.26 μSv/MBq for female subjects and 1.55?±?0.07 μSv/MBq for male subjects. The two organs receiving the highest radiation doses were the urinary bladder (10.81?±?0.23 μGy/MBq and 8.78?±?0.89 μGy/MBq) and the liver (6.80?±?0.78 μGy/MBq and 4.91?±?0.74 μGy/MBq) for female and male subjects, respectively.
Conclusions[11C]Metoclopramide showed predominantly renal excretion, and is safe and well tolerated in healthy adults. The effective dose of [11C]metoclopramide was comparable to other 11C-labeled PET tracers.
相似文献An important issue in rodent imaging is the question whether a mixed population of male and female animals can be used rather than animals of a single sex. For this reason, the present study examined the test-retest stability of positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in male rats and female rats at different phases of the estrous cycle.
ProceduresLong–Evans rats (age 1 year) were divided into three groups: (1) males (n?=?6), (2) females in metestrous (low estrogen levels, n?=?9), and (3) females in proestrous (high estrogen levels, n?=?7). Two standard [18F]FDG scans with rapid arterial blood sampling were made at an interval of 10 days in subjects anesthetized with isoflurane and oxygen. Body temperature, heart rate, and blood oxygenation were continuously monitored. Regional cerebral metabolic rates of glucose were calculated using a Patlak plot with plasma radioactivity as input function.
ResultsRegional metabolic rate of glucose (rCMRglucose) in male and female rats, or [18F]FDG uptake in females at proestrous and metestrous, was not significantly different, but females showed significantly higher standardized uptake values (SUVs) and Patlak flux than males, particularly in the initial scan. The relative difference between the scans and the test-retest variability (TRV) were greater in females than in males. Intra-class correlation coefficients (ICCs) of rCMRglucose, SUV, normalized SUV, and glucose flux were good to excellent in males but poor to moderate in females.
ConclusionsBased on these data for [18F]FDG, the mixing of sexes in imaging studies of the rodent brain will result in an impaired test-retest stability of PET data and a need for larger group sizes to maintain statistical power in group comparisons. The observed differences between males and females do not indicate any specific gender difference in cerebral metabolism but are related to different levels of non-radioactive glucose in blood plasma during isoflurane anesthesia.
相似文献The aim of this study was to evaluate positron emission tomography (PET) imaging with [68Ga]NODAGA-c(RGDfK) ([68Ga]RGD), in comparison with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), for early monitoring of the efficacy of an antiangiogenic agent associated or not with chemotherapy, in a mouse model of glioblastoma (GB).
ProceduresMice bearing U87MG human GB cells line were parted into five groups of five mice each. One group was imaged at baseline before the treatment phase; another group was treated with bevacizumab (BVZ), another group with temozolomide (TMZ), another group with both agents, and the last one was the control group. Tumors growth and biological properties were evaluated by caliper measurements and PET imaging at three time points (baseline, during treatment t1?=?4–6 days and t2?=?10–12 days). At the end of the study, tumors were counted and analyzed by immunohistochemistry (CD31 to evaluate microvessel density).
ResultsThe tumor volume assessed by caliper measurements was significantly greater at t1 in the control group than in the TMZ + BVZ-treated group or in the BVZ-treated group. At t2, tumor volume of all treated groups was significantly smaller than that of the control group. [18F]FDG PET failed to reflect this efficacy of treatment. In contrast, at t1, the [68Ga]RGD tumor uptake was concordant with tumor growth in controls and in treated groups. At t2, a significant increase in tumor uptake of [68Ga]RGD vs. t1 was only observed in the TMZ-treated group, reflecting a lack of angiogenesis inhibition, whereas TMZ + BVZ resulted in a dramatic tumor arrest, reduction in microvessel density and stable tumor [68Ga]RGD uptake.
Conclusions[68Ga]RGD is a useful PET agent for in vivo angiogenesis imaging and can be useful for monitoring antiangiogenic treatment associated or not with chemotherapy.
相似文献To examine the relationships between 2-deoxy-2-[18F]fluoro-d-glucose ([18F]-FDG) and hypoxia tracer [18F]fluoro-azomycinarabinofuranoside ([18F]-FAZA) and between 131I and [18F]-FAZA uptake in patients with metastatic thyroid cancer and to evaluate imaging features associated with short-term progression after 131I therapy.
ProceduresThe study population was 20 patients (17 women and 3 men; mean age, 67 years) with metastatic thyroid cancer who underwent both [18F]-FDG- and [18F]-FAZA-positron emission tomography (PET)/X-ray computed tomography (CT) examinations before 131I therapy. Short-term response to radioiodine was assessed (mean follow-up, 19 months ±?9). PET parameters including [18F]-FDG-SUVmax, [18F]-FAZA-SUVmax, and [18F]-FAZA-tumor-to-muscle [T/M] were obtained. Mann-Whitney U, Wilcoxon signed-rank, or χ2 tests were used to assess differences between two quantitative variables or compare categorical data. Predictive factors for short-term progression were investigated with logistic regression analysis.
ResultsEleven lymph node metastatic lesions were identified in 9 patients and 46 distant metastatic lesions (lung, 19; bone, 17; and liver, 10) in 14 patients. A total of 24 131I-positive and 33 131I-negative lesions were detected. SUVmax was significantly lower with [18F]-FAZA-PET/CT (1.3?±?0.6) than with [18F]-FDG-PET/CT (6.4?±?5.9, p?<?0.001). No significant correlation was observed between [18F]-FAZA-PET/CT and 131I imaging concerning visibility (p?=?0.36). After 131I therapy, 31 of 57 metastatic lesions displayed short-term progression. Multivariate logistic regression revealed that [18F]-FDG-SUVmax (p?=?0.022) and [18F]-FAZA-T/M (p?=?0.002) showed significant associations with short-term progression.
ConclusionsAlthough [18F]-FAZA uptake was low in metastatic thyroid cancers, not only glucose metabolism but also hypoxic conditions may be associated with progression after 131I therapy in patients with metastatic thyroid cancer.
相似文献Evaluation of [68Ga]NODAGA-duramycin as a positron emission tomography (PET) tracer of cell death for whole-body detection of chemotherapy-induced organ toxicity.
ProceduresTracer specificity of Ga-68 labeled NODAGA-duramycin was determined in vitro using competitive binding experiments. Organ uptake was analyzed in untreated and doxorubicin, busulfan, and cisplatin-treated mice 2 h after intravenous injection of [68Ga]NODAGA-duramycin. In vivo data were validated by immunohistology and blood parameters.
ResultsIn vitro experiments confirmed specific binding of [68Ga]NODAGA-duramycin. Organ toxicities were detected successfully using [68Ga]NODAGA-duramycin PET/X-ray computed tomography (CT) and confirmed by immunohistochemistry and blood parameter analysis. Organ toxicities in livers and kidneys showed similar trends in PET/CT and immunohistology. Busulfan and cisplatin-related organ toxicities in heart, liver, and lungs were detected earlier by PET/CT than by blood parameters and immunohistology.
Conclusion[68Ga]NODAGA-duramycin PET/CT was successfully applied to non-invasively detect chemotherapy-induced organ toxicity with high sensitivity in mice. It, therefore, represents a promising alternative to standard toxicological analyses with a high translational potential.
相似文献There are currently no positron emission tomography (PET) radiotracers for the GluN2B (NR2B) binding sites of brain N-methyl-d-aspartate (NMDA) receptors. In rats, the GluN2B antagonist Ro25-6981 reduced the binding of N-((5-(4-fluoro-2-[11C]methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamin ([11C]HACH242). This paper reports the evaluation of [11C]HACH242 PET in non-human primates at baseline and following administration of the GluN2B negative allosteric modulator radiprodil.
ProceduresEight 90-min dynamic [11C]HACH242 PET scans were acquired in three male anaesthetised rhesus monkeys, including a retest session of subject 1, at baseline and 10 min after intravenous 10 mg/kg radiprodil. Standardised uptake values (SUV) were calculated for 9 brain regions. Arterial blood samples were taken at six timepoints to characterise pharmacokinetics in blood and plasma. Reliable input functions for kinetic modelling could not be generated due to variability in the whole-blood radioactivity measurements.
Results[11C]HACH242 entered the brain and displayed fairly uniform uptake. The mean (±?standard deviation, SD) Tmax was 17?±?7 min in baseline scans and 24?±?15 min in radiprodil scans. The rate of radioligand metabolism in plasma (primarily to polar metabolites) was high, with mean parent fractions of 26?±?10 % at 20 min and 8?±?5 % at 85 min. Radiprodil increased [11C]HACH242 whole-brain SUV in the last PET frame by 25 %, 1 %, 3 and 17 % for subjects 1, 2, 3 and retest of subject 1, respectively. The mean brain to plasma ratio was 5.4?±?2.6, and increased by 39 to 110 % in the radiprodil condition, partly due to lower parent plasma radioactivity of ?11 to ?56 %.
ConclusionsThe present results show that [11C]HACH242 has a suitable kinetic profile in the brain and low accumulation of lipophilic radiometabolites. Radiprodil did not consistently change [11C]HACH242 brain uptake. These findings may be explained by variations in cerebral blood flow, a low fraction of specifically bound tracer, or interactions with endogenous NMDA receptor ligands at the binding site. Further experiments of ligand interactions are necessary to facilitate the development of radiotracers for in vivo imaging of the ionotropic NMDA receptor.
相似文献The main purpose of this study was to understand how the positron emission tomography (PET) measure of the synaptic vesicle 2A (SV2A) protein varies in vivo during the development of temporal lobe epilepsy (TLE) in the kainic acid rat model.
ProceduresTwenty Sprague Dawley male rats were administered with multiple systemic doses of saline (control group, n?=?5) or kainic acid (5 mg/kg/injection, epileptic group, n?=?15). Both groups were scanned at the four phases of TLE (early, latent, transition, and chronic phase) with the [18F]UCB-H PET radiotracer and T2-structural magnetic resonance imaging. At the end of the scans (3 months post-status epilepticus), rats were monitored for 7 days with electroencephalography for the detection of spontaneous electrographic seizures. Finally, the immunofluorescence staining for SV2A expression was performed.
ResultsControl rats presented a significant increase in [18F]UCB-H binding at the last two scans, compared with the first ones (p?<?0.001). This increase existed but was lower in epileptic animals, producing significant group differences in all the phases of the disease (p?<?0.028). Furthermore, the quantification of the SV2A expression in vivo with the [18F]UCB-H radiotracer or ex vivo with immunofluorescence led to equivalent results, with a positive correlation between both.
ConclusionsEven if further studies in humans are required, the ability to detect a progressive decrease in SV2A expression during the development of temporal lobe epilepsy supports the use of [18F]UCB-H as a useful tool to differentiate, in vivo, between healthy and epileptic animals along with the development of the epileptic disease.
相似文献Loss of neuronal synapse function is associated with a number of brain disorders. The [11C]UCB-J positron emission tomography (PET) tracer allows for in vivo examination of synaptic density, as it binds to synaptic vesicle glycoprotein 2A (SV2A) expressed in presynaptic terminals. Here, we characterise [11C]UCB-J imaging in Göttingen minipigs.
ProceduresUsing PET imaging, we examined tracer specificity and compared kinetic models. We explored the use of a standard blood curve and centrum semiovale white matter as a reference region. We compared in vivo [11C]UCB-J PET imaging to in vitro autoradiography, Western blotting and real-time quantitative polymerase chain reaction.
ResultsThe uptake kinetics of [11C]UCB-J could be described using a 1-tissue compartment model and blocking of SV2A availability with levetiracetam showed dose-dependent specific binding. Population-based blood curves resulted in reliable [11C]UCB-J binding estimates, while it was not possible to use centrum semiovale white matter as a non-specific reference region. Brain [11C]UCB-J PET signals correlated well with [3H]UCB-J autoradiography and SV2A protein levels.
Conclusions[11C]UCB-J PET is a valid in vivo marker of synaptic density in the minipig brain, with binding values close to those reported for humans. Minipig models of disease could be valuable for investigating the efficacy of putative neuroprotective agents for preserving synaptic function in future non-invasive, longitudinal studies.
相似文献We tested whether the translocator protein (TSPO)-targeted positron emission tomography (PET) tracer, N-acetyl-N-(2-[11C]methoxybenzyl)-2-phenoxy-5-pyridinamine ([11C]PBR28), could distinguish macrophage dominant from neutrophilic inflammation better than 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in mouse models of lung inflammation and assessed TSPO association with macrophages in lung tissue from the mouse models and in patients with chronic obstructive pulmonary disease (COPD).
ProceduresMicroPET imaging quantified [11C]PBR28 and [18F]FDG lung uptake in wild-type (Wt) C57BL/6J or heterozygous transgenic monocyte-deficient Wt/opT mice at 49 days after Sendai virus (SeV) infection, during macrophage-dominant inflammation, and in Wt mice at 3 days after SeV infection or 24 h after endotoxin instillation during neutrophilic inflammation. Immunohistochemical staining for TSPO in macrophages and neutrophils was performed using Mac3 and Ly6G for cell identification in mouse lung sections and CD68 and neutrophil elastase (NE) in human lung sections taken from explanted lungs from patients with COPD undergoing lung transplantation and donor lungs rejected for transplantation. Differences in tracer uptake among SeV-infected, endotoxin-treated, and uninfected/untreated control mice and in TSPO staining between neutrophils and macrophage populations in human lung sections were tested using analysis of variance.
ResultsIn Wt mice, [11C]PBR28 uptake (% injected dose/ml lung tissue) increased significantly with macrophage-dominant inflammation at 49 days (D49) after SeV infection compared to controls (p = <0.001) but not at 3 days (D49) after SeV infection (p = 0.167). [11C]PBR28 uptake was unchanged at 24 h after endotoxin instillation (p = 0.958). [18F]FDG uptake increased to a similar degree in D3 and D49 SeV-infected and endotoxin-treated Wt mice compared to controls with no significant difference in the degree of increase among the tested conditions. [11C]PBR28 but not [18F]FDG lung uptake at D49 post-SeV infection was attenuated in Wt/opT mice compared to Wt mice. TSPO localized predominantly to macrophages in mouse lung tissue by immunostaining, and TSPO staining intensity was significantly higher in CD68+ cells compared to neutrophils in the human lung sections.
ConclusionsPET imaging with [11C]PBR28 can specifically detect macrophages versus neutrophils during lung inflammation and may be a useful biomarker of macrophage accumulation in lung disease.
相似文献To assess the diagnostic performance of simultaneous whole-body 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) compared to [18F]FDG PET/x-ray computed tomography (CT) for detection of distant metastatic disease in patients with malignant melanoma.
ProceduresWe included patients with malignant melanoma who underwent a single injection [18F]FDG dual-imaging protocol that included whole-body PET/CT and subsequent whole-body PET/MRI for staging or restaging purposes in a prospective setting. Images from both modalities were analyzed by two rater teams for the presence of metastatic lesions. PET/CT–PET/MRI overall agreement as well as region-based accuracies, sensitivities (Se), and specificities (Sp) were computed.
ResultsBetween July 2014 and December 2018, 22 patients were enrolled. Interrater agreement and overall accuracy (consensus reading) were 78.8 % (95 % CI 71–84.9) and 96.1 % (95 % CI 92.3–98) for PET/MRI and 78 % (70.2–84.3) and 97.4 % (95 % CI 93.7–98.9) for PET/CT, respectively (P?=?0.42). PET/MRI reached a region-based Se of 89.1 % (95 % CI 79.4–94.5) and a Sp of 100 %, whereas PET/CT showed a region-based Se of 92.7 % (95 % CI 84–96.9) and a Sp of 100 % for the detection of metastatic disease in malignant melanoma.
ConclusionsWhole-body [18F]FDG-PET/MRI appears to be comparable to [18F]FDG-PET/CT for lesion detection in patients with malignant melanoma.
相似文献