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In this study, we aimed to quantitatively investigate the biodistribution of [18F]DCFPyL in patients with prostate cancer (PCa) and to determine whether uptake in normal organs correlates with an increase in tumor burden.
ProceduresFifty patients who had been imaged with [18F]DCFPyL positron emission tomography/computed tomography (PET/CT) were retrospectively included in this study. Forty of 50 (80 %) demonstrated radiotracer uptake on [18F]DCFPyL PET/CT compatible with sites of PCa. Volumes of interests (VOIs) were set on normal organs (lacrimal glands, parotid glands, submandibular glands, liver, spleen, and kidneys) and on tumor lesions. Mean standardized uptake values corrected to lean body mass (SULmean) and mean standardized uptake values corrected to body weight (SUVmean) for normal organs were assessed. For the entire tumor burden, SULmean/max, SUVmean, tumor volume (TV), and the total activity in the VOI were obtained using tumor segmentation. A Spearman’s rank correlation coefficient was used to investigate correlations between normal organ uptake and tumor burden.
ResultsThere was no significant correlation between TV with the vast majority of the investigated organs (lacrimal glands, parotid glands, submandibular glands, spleen, and liver). Only the kidney showed significant correlation: With an isocontour threshold at 50 %, left kidney uptake parameters correlated significantly with TV (SUVmean, ρ?=???0.214 and SULmean, ρ?=???0.176, p?<?0.05, respectively).
ConclusionsOnly a minimal sink effect with high tumor burden in patients imaged with [18F]DCFPyL was observed. Other factors, such as a high intra-patient variability of normal organ uptake, may be a much more important consideration for personalized dosimetry with PSMA-targeted therapeutic agents structurally related to [18F]DCFPyL than the tumor burden.
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Purpose
To provide clinically useful gadolinium-free whole-body cancer staging of children and young adults with integrated positron emission tomography/magnetic resonance (PET/MR) imaging in less than 1 h.Procedures
In this prospective clinical trial, 20 children and young adults (11–30 years old, 6 male, 14 female) with solid tumors underwent 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) PET/MR on a 3T PET/MR scanner after intravenous injection of ferumoxytol (5 mg Fe/kg) and [18F]FDG (2–3 MBq/kg). Time needed for patient preparation, PET/MR image acquisition, and data processing was compared before (n = 5) and after (n = 15) time-saving interventions, using a Wilcoxon test. The ferumoxytol-enhanced PET/MR images were compared with clinical standard staging tests regarding radiation exposure and tumor staging results, using Fisher’s exact tests.Results
Tailored workflows significantly reduced scan times from 36 to 24 min for head to mid thigh scans (p < 0.001). These streamlined PET/MR scans were obtained with significantly reduced radiation exposure (mean 3.4 mSv) compared to PET/CT with diagnostic CT (mean 13.1 mSv; p = 0.003). Using the iron supplement ferumoxytol “off label” as an MR contrast agent avoided gadolinium chelate administration. The ferumoxytol-enhanced PET/MR scans provided equal or superior tumor staging results compared to clinical standard tests in 17 out of 20 patients. Compared to PET/CT, PET/MR had comparable detection rates for pulmonary nodules with diameters of equal or greater than 5 mm (94 vs. 100 %), yet detected significantly fewer nodules with diameters of less than 5 mm (20 vs 100 %) (p = 0.03). [18F]FDG-avid nodules were detected with slightly higher sensitivity on the PET of the PET/MR compared to the PET of the PET/CT (59 vs 49 %).Conclusion
Our streamlined ferumoxytol-enhanced PET/MR protocol provided cancer staging of children and young adults in less than 1 h with equivalent or superior clinical information compared to clinical standard staging tests. The detection of small pulmonary nodules with PET/MR needs to be improved.Existing clinical or microbiological scores are not sensitive enough to obtain prompt identification of patients at risk of complicated Clostridium difficile infection (CDI). Our aim was to use a CDI animal model to evaluate 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG-PET) as a marker of severe course of infection.
ProceduresCDI was induced with cefoperazone for 10 days followed by clindamycin 1 day before C. difficile inoculation. Mice were divided into wild type (n?=?6), antibiotic without infection (AC n?=?4), h001-infected (n?=?5, ribotype 001), and h027-infected (n?=?5, ribotype 027). Two days after inoculation, [18F]FDG-PET was acquired. Weight, general animal condition, and survival were monitored daily for 9 days.
Resultsh001 group showed symptoms for 4 days with 0 % mortality and a similar colon uptake than control animals (h001 0.52?±?0.20, WT 0.42?±?0.07, and AC 0.36?±?0.06). The h027 group showed symptoms up to 7 days, with 66.7 % of mortality 4 days after infection, and significantly higher colon uptake (0.93?±?0.38, p?<?0.05). Clinical score was associated to colon and cecum uptake (rho?=?0.78, p?=?0.0001) (rho?=?0.73, p?=?0.0003).
ConclusionHigh toxin producer ribotype 027 induced more severe CDI infections, correlating with higher colon and cecum [18F]FDG uptake. Colon uptake may purportedly serve as early predictor of CDI severity.
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
The purpose of this study was to compare and correlate standardized uptake values (SUV) derived from magnetic resonance attenuation correction (MRAC) with those derived from computed tomography attenuation correction (CTAC) in an oncology patient population.Procedures
The HIPAA-compliant study was approved by the Internal Review Board and all subjects gave written informed consent prior to inclusion in the study. Forty patients (mean age 61?±?15.1; 20 male) referred for clinically indicated 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) scans also underwent a PET/magnetic resonance imaging (MRI) examination. MRAC was performed using an automatic three-segment model. Regions of interest were drawn over eight normal structures in order to obtain SUVmax and SUVmean values. Spearman rank correlation coefficients (r) were calculated and two-tailed paired t tests were performed to compare the SUVmax and SUVmean values obtained from CTAC with those from MRAC.Results
The mean time after FDG injection was 66?±?7 min for PET/CT and 117?±?15 min for PET/MRI examination. MRAC SUV values were significantly lower than the CTAC SUV values in mediastinal blood pool (p?<?0.001 for both SUVmax and SUVmean) and liver (p?=?0.01 for SUVmean). The MRAC SUV values were significantly higher in bone marrow (p?<?0.001 for both SUVmax and SUVmean), psoas major muscle (p?<?0.001 for SUVmax), and left ventricular myocardium (p?<?0.001 for SUVmax and p?=?0.01 for SUVmean). For the other normal structures, no significant difference was observed. When comparing SUV values generated from CTAC versus MRAC, high correlations between CTAC and MRAC were observed in myocardium (r?=?0.96/0.97 for SUVmax/mean), liver (r?=?0.68 for SUVmax), bone marrow (r?=?0.80/0.83 for SUVmax/mean), lung tissue (r?=?0.70 for SUVmax), and mediastinal blood pool (r?=?0.0.68/.069 for SUVmax/mean). Moderate correlations were found in lung tissue (r?=?0.67 for SUV mean), liver (r?=?0.66 for SUVmean), fat (r?=?0.48/0.53 for SUVmax/mean), psoas major muscle (r?=?0.54/0.58 for SUVmax/mean), and iliacus muscle (r?=?0.41 for SUVmax). Low correlation was found in iliacus muscle (r?=?0.32 for SUVmean).Conclusions
Using the automatic three-segment model, our study showed high correlation for measurement of SUV values obtained from MRAC compared to those from CTAC, as the reference standard. Differences observed between MRAC and CTAC derived SUV values may be attributed to the time-delay between the PET/CT and PET/MRI scans or biologic clearance of radiotracer. Further studies are required to assess SUV measurements when performing different MR attenuation correction techniques. 相似文献SimPET/M7 system is a small-animal dedicated simultaneous positron emission tomography and magnetic resonance imaging (PET/MRI) scanner. The SimPET insert has been upgraded from its prototype with a focus on count rate performance and sensitivity. The M7 scanner is a 1-T permanent magnet-based compact MRI system without any cryogens. Here, we present performance evaluation results of SimPET along with the results of mutual interference evaluation and simultaneously acquired PET/MR imaging.
ProceduresFollowing NEMA NU 4-2008 standard, we evaluated the performance of the SimPET system. The M7 MRI compatibility of SimPET was also assessed by analyzing MRI images of a uniform phantom under different PET conditions and PET count rates with different MRI pulse sequences. Mouse imaging was performed including a whole-body 18F-NaF PET scan and a simultaneous PET/MRI scan with 64Cu-NOTA-ironoxide.
ResultsThe spatial resolution at center based on 3D OSEM without and with warm background was 0.7 mm and 1.45 mm, respectively. Peak sensitivity was 4.21 % (energy window?=?250–750 keV). The peak noise equivalent count rate with the same energy window was 151 kcps at 38.4 MBq. The uniformity was 4.42 %, and the spillover ratios in water- and air-filled chambers were 14.6 % and 12.7 %, respectively. In the hot rod phantom image, 0.75-mm-diameter rods were distinguishable. There were no remarkable differences in the SNR and uniformity of MRI images and PET count rates with different PET conditions and MRI pulse sequences. In the whole-body 18F-NaF PET images, fine skeletal structures were well resolved. In the simultaneous PET/MRI study with 64Cu-NOTA-ironoxide, both PET and MRI signals changed before and after injection of the dual-modal imaging probe, which was evident with the exact spatiotemporal correlation.
ConclusionsWe demonstrated that the SimPET scanner has a high count rate performance and excellent spatial resolution. The combined SimPET/M7 enabled simultaneous PET/MR imaging studies with no remarkable mutual interference between the two imaging modalities.
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The purpose of the study was to assess the feasibility and diagnostic performance of FDG-PET/MR imaging compared to PET/CT for staging of patients with a gynecological malignancy.
Methods25 patients with a gynecological malignancy were prospectively enrolled into this pilot study. Patients underwent sequential full-body PET/CT and PET/MR of the abdomen and pelvis after administration of a single dose of F-18 FDG. PET/MRI and PET/CT images were independently reviewed by two expert radiologists. Readers were blinded to the results of the other imaging procedures. Clinical and pathologic information was abstracted from medical charts.
Results18 patients were included in the final analysis with a median age of 62 years (range 31–88). 61% of patients (11/18) had cervical cancer, while the remaining patients had endometrial cancer. PET/MRI as compared to PET/CT detected all primary tumors, 7/7 patients with regional lymph nodes, and 1/1 patient with an abdominal metastasis. Two patients had additional lymph nodes outside of the abdominopelvic cavity detected on PET/CT that were not seen on PET/MRI, whereas 6 patients had parametrial invasion and one patient had invasion of the bladder seen on PET/MRI not detected on PET/CT. Five cervical cancer patients had discordant clinical vs. radiographic staging based on PET/MRI detection of soft tissue involvement. Management changed for two patients who had clinical stage IB1 and radiographic stage IIB cervical cancer.
ConclusionsPET/MRI is feasible and has at least comparable diagnostic ability to PET/CT for identification of primary cervical and endometrial tumors and regional metastases. PET/MRI may be superior to PET/CT for initial radiographic assessment of cervical cancers.
相似文献The aim of this study was to optimize the radiolabeling method of [18F]fluoropropyl-(+)-dihydrotetrabenazine ([18F]FP-(+)-DTBZ) to fulfill the demand of preclinical and clinical application.
ProceduresOptimized labeling conditions were performed by altering the molar ratio of precursor to base (P/B), base species, solvents, reaction temperature, reaction time, and precursor concentration through manual radiosynthesis of [18F]FP-(+)-DTBZ. The conditions with the highest radiochemical yield (RCY) were applied to automated radiosynthesis, and the crude product was purified with a Sep-Pak Plus C18 cartridge. Quality control and stability of [18F]FP-(+)-DTBZ were carried out by HPLC. In vitro cellular uptake and blocking assays were conducted in human neuroblastoma cell line SH-SY5Y. In vivo imaging with small animal positron emission tomography (microPET) was performed with Sprague–Dawley rats.
ResultsUnder the optimized conditions (P/K2CO3?=?1:8, heating at 120 °C for 3 min in dimethyl sulfoxide), an RCY of 88.7 % was obtained with 1.0 mg precursor. The optimized reaction conditions were successfully applied to an automated module and gave a high activity yield (AY) of 30–55 % in about 40 min with a >?99.0 % radiochemical purity (RCP) and a >?44.4 GBq/μmol molar activity (Am). Stability test displayed that the RCP retained >?98.0 % in 8 h in saline and in phosphate buffer saline (PBS, pH 7.4). In vitro cellular uptake assay showed accumulation of [18F]FP-(+)-DTBZ in SH-SY5Y cells, which could be significantly inhibited by vesicular monoamine transporter 2 (VMAT2) inhibitor DTBZ. MicroPET images of rat brain displayed that the striatum showed the highest uptake with a standardized uptake value (SUV) of 3.91?±?0.30 at ~?70 min. Co-injection with DTBZ (1.0 mg/kg) resulted in a 75 % decrease of the striatal SUV, confirming the specificity of [18F]FP-(+)-DTBZ to VMAT2.
ConclusionsWe obtained an optimized radiolabeling method of [18F]FP-(+)-DTBZ and successfully applied it to a commercial available module. The automated synthesis gave a high AY and RCP of [18F]FP-(+)-DTBZ with high and specific binding to VMAT2, facilitating its routine application for VMAT2 tracing.
相似文献The glutamine analogue (2S, 4R)-4-[18F]fluoroglutamine ([18F]FGln) was investigated to further characterize its pharmacokinetics and acquire in vivo positron emission tomography (PET) images of separate orthotopic and subcutaneous glioma xenografts in mice.
Procedures[18F]FGln was synthesized at a high radiochemical purity as analyzed by high-performance liquid chromatography. An orthotopic model was created by injecting luciferase-expressing patient-derived BT3 glioma cells into the right hemisphere of BALB/cOlaHsd-Foxn1nu mouse brains (tumor growth monitored via in vivo bioluminescence), the subcutaneous model by injecting rat BT4C glioma cells into the flank and neck regions of Foxn1nu/nu mice. Dynamic PET images were acquired after injecting 10–12 MBq of the tracer into mouse tail veins. Animals were sacrificed 63 min after tracer injection, and ex vivo biodistributions were measured. Tumors and whole brains (with tumors) were cryosectioned, autoradiographed, and stained with hematoxylin-eosin. All images were analyzed with CARIMAS software. Blood sampling of 6 Foxn1nu/nu and 6 C57BL/6J mice was performed after 9–14 MBq of tracer was injected at time points between 5 and 60 min then assayed for erythrocyte uptake, plasma protein binding, and plasma parent-fraction of radioactivity to correct PET image-derived whole-blood radioactivity and apply the data to multiple pharmacokinetic models.
ResultsOrthotopic human glioma xenografts displayed PET image tumor-to-healthy brain region ratio of 3.6 and 4.8 while subcutaneously xenografted BT4C gliomas displayed (n?=?12) a tumor-to-muscle (flank) ratio of 1.9?±?0.7 (range 1.3–3.4). Using PET image-derived blood radioactivity corrected by population-based stability analyses, tumor uptake pharmacokinetics fit Logan and Yokoi modeling for reversible uptake.
ConclusionsThe results reinforce that [18F]FGln has preferential uptake in glioma tissue versus that of corresponding healthy tissue and fits well with reversible uptake models.
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