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1.
Lipid nanoparticles (LNPs) are becoming popular as a means of delivering therapeutics, including those based on nucleic acids and mRNA. The mRNA-based coronavirus disease 2019 vaccines are perfect examples to highlight the role played by drug delivery systems in advancing human health. The fundamentals of LNPs for the delivery of nucleic acid- and mRNA-based therapeutics, are well established. Thus, future research on LNPs will focus on addressing the following: expanding the scope of drug delivery to different constituents of the human body, expanding the number of diseases that can be targeted, and studying the change in the pharmacokinetics of LNPs under physiological and pathological conditions. This review article provides an overview of recent advances aimed at expanding the application of LNPs, focusing on the pharmacokinetics and advantages of LNPs. In addition, analytical techniques, library construction and screening, rational design, active targeting, and applicability to gene editing therapy have also been discussed. 相似文献
2.
3.
Mhamed 《Computerized medical imaging and graphics》2006,30(8):447-451
The aim in this work is to report a new method to calculate parametric images from a single scan acquisition with positron emission tomography (PET) and fluorodeoxyglucose (FDG) in the human brain without blood sampling. It is usually practical for research or clinical purposes to inject the patient in an isolated room and to start the PET acquisition only for some 10–20 min, about 30 min after FDG injection. In order to calculate the cerebral metabolic rates for glucose (CMRG), usually several blood samples are required. The proposed method considers the relation between the uptake of the tracer in the cerebellum as a reference tissue and the population based input curve. Similar results were obtained for CMRG values with the present method in comparison to the usual autoradiographic and the non-linear least squares fitting of regions of interest. 相似文献
4.
Kazuhiko Yanai Tatsuo Ido Kiichi Ishiwata Jun Hatazawa Toshihiro Takahashi Ren Iwata Taiju Matsuzawa 《European journal of nuclear medicine and molecular imaging》1986,12(3):141-146
The endogenous hallucinogen, N,N-dimethyltryptamine (DMT), was labeled with carbon-11 and its regional distribution in rat brain studied. [11C]DMT showed higher accumulation in the cerebral cortex, caudate putamen, and amygdaloid nuclei. Studies of the subcellular distribution of [11C]DMT revealed the specific localization in the fractions enriched with serotonin receptors only when a very low dose was injected into rats. The proportions of the radioactivity in receptor-rich fractions were greatly enhanced by pretreatment with the monoamine oxidase inhibitor, pargyline. Specific binding of [11C]DMT to serotonin receptors in dog brain was demonstrated by a positron emission tomographic study in which 5-methoxy-N,N-dimethyltryptamine caused approximately 20% displacement of the radioligand from the receptors. 相似文献
5.
M. Bergström G. Westerberg G. Németh M. Traut G. Gross G. Greger H. Müller-Peltzer A. Safer S.-Å. Eckernäs A. Grahnér B. Långström 《European journal of clinical pharmacology》1997,52(2):121-128
Objective: The aim of the study was to investigate whether or not esuprone binds substantially to MAO-A in the human brain. Methods: In a randomised double-blind placebo-controlled study 16 male healthy volunteers were examined␣with positron emission tomography
(PET) with [11C]harmine. Eight of the volunteers were given daily doses of 800 mg esuprone, four were given bi-daily doses of 300 mg moclobemide,
and four volunteers were given placebo tablets. PET was performed before initiation of a 7-day treatment period. On day 7,
one investigation was made immediately before administration of the drug, representing 23 h after the previous day's treatment
for esuprone and 11 h after the last tablets of moclobemide. Further investigations were made 4 h and 8 h after the morning
dose on day 7. Results: PET showed a high degree of binding of [11C]harmine, a high-affinity ligand for MAO-A, before the start of treatment, and a marked and similar reduction after treatment
with esuprone and moclobemide. A slight tendency for normalisation of enzyme binding was observed at the last time point.
In the placebo group no change was observed. Plasma kinetics of esuprone showed a rapid elimination with a half-life of about
4 h. Conclusion: The study demonstrates that esuprone was comparable to moclobemide in its effect on MAO-A inhibition in the brain at the
doses given. This is an illustration of the potential of PET to monitor drug effects directly on target biochemical systems
in the brain in human volunteers, and the possibility of using these data, rather than pharmacokinetic data, for the determination
of dosing intervals.
Received: 21 August 1996 / Accepted in revised form: 22 November 1996 相似文献
6.
Annemieke C. Kole MD Omgo E. Nieweg MD PhD Robert J. van Ginkel MD Jan Pruim MD PhD Harald J. Hoekstra MD PhD Anne M. J. Paans PhD Willem Vaalburg PhD Dr. Heimen Schraffordt Koops MD PhD 《Annals of surgical oncology》1997,4(1):57-63
Background: It is often difficult to detect a local recurrence of soft-tissue sarcomas due to disturbance of the normal anatomy by previous
surgery and radiotherapy. The aim of this study was to assess the value of positron emission tomography (PET) with [18F]fluoro-2-deoxy-d-glucose (FDG) for detecting local recurrences.
Methods: In the period 1992–1995, 17 patients with proven or suspected local recurrence of soft-tissue sarcoma were examined using
FDG-PET. Fifteen of these patients were ultimately proven to have a recurrence.
Results: Recurrence was visualized in 14 patients (93%). Small tumors (maximum diameter 0.5 cm) were as easily visible as large lesions
(maximum diameter 20 cm). In one patient the PET scan was positive, but the recurrence could not be proven histologically.
Recurrence was proven 1 year later. A recurrent low-grade liposarcoma was not visualized. The two patients with benign lesions
had a negative PET scan. The mean glucose metabolic rate was calculated to be 13.2 μmol/100 g/min (range 1.9–28.4). A correlation
was found between the histological malignancy grade and the metabolic rate (p<0.05; Kruskal-Wallis).
Conclusion: PET with FDG is a useful addition to the diagnostic armamentarium for detecting local recurrence of soft-tissue sarcomas
and provides an indication of the malignancy grade of the recurrent lesion.
Presented at the 47th Annual Meeting of The Society for Surgical Oncology, Houston, Texas, March 17–20, 1994. 相似文献
7.
8.
Coronary vasomotion in patients with syndrome X: evaluation with positron emission tomography and parametric myocardial perfusion imaging 总被引:1,自引:1,他引:0
Joan G. Meeder Paul K. Blanksma Ernst E. van der Wall Antoon T. M. Willemsen Jan Pruim Rutger L. Anthonio Richard M. de Jong Willem Vaalburg Kong I. Lie 《European journal of nuclear medicine and molecular imaging》1997,24(5):530-537
The aim of this study was to elucidate further the causative mechanism of abnormal coronary vasomotion in patients with syndrome X. In patients with syndrome X, defined as angina pectoris and documented myocardial ischaemia during stress testing with normal findings at coronary angiography, abnormal coronary vasomotion of either the micro- or the macrocirculation has been suggested as the causative mechanism. Accordingly, we evaluated endothelial function, vasodilator reserve, and perfusion heterogeneity in these patients. Twenty-five patients with syndrome X (definitely normal coronary arteriogram, group A), 15 patients with minimal coronary artery disease (group B) and 21 healthy volunteers underwent [13N]ammonia positron emission tomography at rest, during cold pressor stimulation (endothelial function) and during dipyridamole stress testing (vasodilator reserve). Heterogeneity of myocardial perfusion was analysed by parametric polar mapping using a 480-segment model. In both patient groups, resting perfusion was increased compared to the normal subjects: group A, 127±31 ml·min–1·100 g–1; group B, 124±30 ml·min–1·100 g–1 normal subjects, 105±21 ml·min–1·100 g–1 (groups A and B vs normals,P<0.05). These differences were abolished after correction for rate-pressure product. During cold pressor stimulation, the perfusion responses (ratio of cold pressor perfusion to resting perfusion) were similar among the patients and the control subjects (group A, 1.20±0.23; group B, 1.24±0.22; normal subjects, 1.23±0.14). Likewise, during dipyridamole stress testing, perfusion responses were similar among the three groups (group A, 2.71±0.67; group B, 2.77±1.29; normal subjects, 2.91±1.04). In group A the heterogeneity of resting perfusion, expressed as coefficient of variation, was significantly different from the volunteers (20.1±4.5 vs 17.0±3.0,P<0.05). In group B (coefficient of variation 19.4±3.9) the difference from normal volunteers was not significant. In this study, patients with syndrome X and patients with minimal coronary artery disease showed normal perfusion responses during cold pressor stimulation and dipyridamole stress testing. Our findings therefore suggest that endothelial dysfunction and impaired vasodilator reserve are of no major pathophysiological relevance in patients with syndrome X. Rather, other mechanisms such as increased sympathetic tone and focal release of vasoactive substances may play a role in the pathogenesis of syndrome X. 相似文献
9.
Zubin Bhagwagar Andrew J Montgomery Paul M Grasby Philip J Cowen 《Neuropsychopharmacology》2003,54(9):890-895
BACKGROUND: Elevated cortisol levels might account for the reduction in central serotonin 1A (5-hydroxytryptamine [5-HT](1A)) receptor binding and function observed in patients with major depression. We tested this hypothesis by studying the effect of acute administration of hydrocortisone on 5-HT(1A) receptor binding potential (BP) in subjects recovered from depression. METHODS: We studied 14 subjects (8 male, 6 female) who had recovered from at least two episodes of major depression and had been euthymic and drug free for at least 6 months. Serotonin 1A receptor BP was measured by [(11)C]WAY-100635 in conjunction with positron emission tomography. Subjects were tested on two occasions in a double-blind, random-order, crossover design after administration of either hydrocortisone (100 mg orally) or placebo 12 hours previously. Positron emission tomography scans were analyzed with a region of interest analysis. RESULTS: Hydrocortisone treatment did not decrease 5-HT(1A) receptor BP either in the hippocampus, which was our a priori hypothesis, or in other cortical 5-HT(1A) regions; however, female subjects had a higher 5-HT(1A) receptor BP in certain brain areas compared with male subjects. CONCLUSIONS: These data are consistent with an earlier study in healthy volunteers and do not support the proposal that decreased 5-HT(1A) receptor BP in patients with acute major depression is a consequence of cortisol hypersecretion. 相似文献
10.
Per Hartvig S.Å. Eckernäs Leif Lindström Bengt Ekblom Ulf Bondesson Hans Lundqvist Christer Halldin Kjell Någren Bengt Långström 《Psychopharmacology》1986,89(2):248-252
By means of positron emission tomography the uptake and kinetics of N-(methyl-11C)clozapine in different brain regions have been studied in Rhesus monkeys. 11C-clozapine rapidly entered the brain and maximum radioactive uptake was seen 5–12 min after administration. Highest uptake was measured in the striatum. Other regions with an uptake higher than in the cerebellum were thalamus and mesencephalon. The radioactivity from different brain regions decreased with an elimination half-life of about 5 h and parallelled the plasma kinetics of unlabelled clozapine. The striatum/cerebellum ratio of 11C-clozapine-derived radioactivity remained constant during the period studied and did not change after pretreatment with atropine. In contrast, the striatum/cerebellum ratio was somewhat lower after pretreatment with N-methylspiperone (NMSP), indicating competition for the same binding sites in the striatum. After pretreatment with increasing doses of clozapine, a dose-dependent protection of binding sites in the striatum for 11C-NMSP was seen. It is concluded that clozapine is more loosely bound to dopamine receptors in the striatum than N-methylspiperone and that the kinetics of clozapine in the brain parallel that in the plasma. The binding properties of clozapine within the brain may explain some of the clinical properties of the drug. 相似文献