scholarly journals Kinetic Modelling of [68Ga]Ga-DOTA-Siglec-9 in Porcine Osteomyelitis and Soft Tissue Infections

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4094 ◽  
Author(s):  
Lars Jødal ◽  
Anne Roivainen ◽  
Vesa Oikonen ◽  
Sirpa Jalkanen ◽  
Søren B. Hansen ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Hind Limb ◽  
Kinetic Modelling ◽  
Compartment Model ◽  
Cell Surface Expression ◽  
Soft Tissue Infections ◽  
Tissue Samples ◽  
Tissue Compartment ◽  
Arterial Blood ◽  
Kinetics Of

Background: [68Ga]Ga-DOTA-Siglec-9 is a positron emission tomography (PET) radioligand for vascular adhesion protein 1 (VAP-1), a protein involved in leukocyte trafficking. The tracer facilitates the imaging of inflammation and infection. Here, we studied the pharmacokinetic modelling of [68Ga]Ga-DOTA-Siglec-9 in osteomyelitis and soft tissue infections in pigs. Methods: Eight pigs with osteomyelitis and soft tissue infections in the right hind limb were dynamically PET scanned for 60 min along with arterial blood sampling. The fraction of radioactivity in the blood accounted for by the parent tracer was evaluated with radio-high-performance liquid chromatography. One- and two-tissue compartment models were used for pharmacokinetic evaluation. Post-mortem soft tissue samples from one pig were analysed with anti-VAP-1 immunofluorescence. In each analysis, the animal’s non-infected left hind limb was used as a control. Results: Tracer uptake was elevated in soft tissue infections but remained low in osteomyelitis. The kinetics of [68Ga]Ga-DOTA-Siglec-9 followed a reversible 2-tissue compartment model. The tracer metabolized quickly; however, taking this into account, produced more ambiguous results. Infected soft tissue samples showed endothelial cell surface expression of the Siglec-9 receptor VAP-1. Conclusion: The kinetics of [68Ga]Ga-DOTA-Siglec-9 uptake in porcine soft tissue infections are best described by the 2-tissue compartment model.

Quantification of Cerebral A1 Adenosine Receptors in Humans using [18F]CPFPX and PET

2004 ◽  
Vol 24 (3) ◽  
pp. 323-333 ◽  
Author(s):  
Philipp T Meyer ◽  
Dirk Bier ◽  
Marcus H Holschbach ◽  
Christian Boy ◽  
Ray A Olsson ◽  
...  
Keyword(s):  
Compartment Model ◽  
Graphical Analysis ◽  
Attractive Alternative ◽  
The Novel ◽  
Tissue Compartment ◽  
Arterial Blood ◽  
Positron Emission ◽  
Pet Scanning ◽  
Kinetics Of

Adenosine is an important neuromodulator. Basic cerebral effects of adenosine are exerted by the A1 adenosine receptor (A1AR), which is accessible in vivo by the novel ligand [18F]8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine ([18F]CPFPX) and positron emission tomography (PET). The present study investigates the applicability of kinetic models to describe the cerebral kinetics of [18F]CPFPX in order to quantify A1AR density in vivo. Six healthy volunteers underwent dynamic PET scanning and arterial blood sampling after bolus injection of [18F]CPFPX. For quantitative analysis, a standard two-tissue compartment model (2TCM) was compared with a one-tissue compartment model (1TCM) and Logan's graphical analysis (GA). The 2TCM described the cerebral kinetics of [18F]CPFPX significantly better than the 1TCM (in all regions and subjects examined). The estimated values of the regional total distribution volumes ( DVt) correlated strongly between the 2TCM and GA (linear regression r2 = 0.99, slope: 1.007). The DVt correlation between the 2TCM and the 1TCM was comparably high, but there was a significant bias towards lower DVt estimates given by the 1TCM (r2: 0.99, slope: 0.929). It is concluded that a 2TCM satisfactorily accounts for the cerebral kinetics of [18F]CPFPX. GA represents an attractive alternative method of analysis.

scholarly journals Kinetic Analysis of the 5-HT2A Ligand [11C]MDL 100,907

2000 ◽  
Vol 20 (6) ◽  
pp. 899-909 ◽  
Author(s):  
Hiroshi Watabe ◽  
Michael A. Channing ◽  
Margaret G. Der ◽  
H. Richard Adams ◽  
Elaine Jagoda ◽  
...  
Keyword(s):  
Kinetic Analysis ◽  
Specific Binding ◽  
Compartment Model ◽  
Input Function ◽  
Brain Regions ◽  
Time Activity ◽  
Tissue Compartment ◽  
Arterial Blood ◽  
Fixed Parameter ◽  
Mdl 100,907

The goal of this study was to develop a suitable kinetic analysis method for quantification of 5-HT2A receptor parameters with [11C]MDL 100,907. Twelve control studies and four preblocking studies (400 nmol/kg unlabeled MDL 100,907) were performed in isoflurane-anesthetized rhesus monkeys. The plasma input function was determined from arterial blood samples with metabolite measurements by extraction in ethyl acetate. The preblocking studies showed that a two-tissue compartment model was necessary to fit the time activity curves of all brain regions including the cerebellum—in other words, the need for two compartments is not proof of specific binding. Therefore, a three-tissue compartment model was used to analyze the control studies, with three parameters fixed based on the preblocking data. Reliable fits of control data could be obtained only if no more than three parameters were allowed to vary. For routine use of [11C]MDL 100,907, several simplified methods were evaluated. A two-tissue (2T‘) compartment with one fixed parameter was the most reliable compartmental approach; a one-compartment model failed to fit the data adequately. The Logan graphical approach was also tested and produced comparable results to the 2T’ model. However, a simulation study showed that Logan analysis produced a larger bias at higher noise levels. Thus, the 2T' model is the best choice for analysis of [11C]MDL 100,907 studies.

Measuring tracee turnover from tracer specific activity in the steady state

1988 ◽  
Vol 255 (1) ◽  
pp. E94-E98 ◽  
Author(s):  
S. L. Lehman ◽  
W. C. Stanley
Keyword(s):  
Steady State ◽  
Specific Activity ◽  
Numerical Estimate ◽  
Venous Blood ◽  
Compartment Model ◽  
Tissue Specific ◽  
Tissue Compartment ◽  
Arterial Blood ◽  
The Difference ◽  
Relationship Of

When a substrate appears in and disappears from an unmeasured (tissue) compartment, the proper sites for tracer infusion and sampling to measure tracee turnover become controversial. We analyze a three-compartment model representing arterial blood, tissue, and venous blood. The desired quantity, tracee turnover, is the ratio of the steady-state infusion rate to tissue specific activity. However, specific activity in the tissue compartment is unknown. We assume infusion of tracer into the arterial pool at a constant rate and consider sampling of specific activity of either blood compartment in the steady state. We obtain estimates of tissue specific activity from measurement of concentrations of tracer and tracee in blood samples in two extreme cases. In case I, tracee is assumed to appear in the venous compartment but to disappear from the tissue pool. Then tissue specific activity is equal to arterial specific activity. In case II, both appearance and disappearance are from the tissue pool. Tissue specific activity is then less than arterial or venous specific activity. We give formulas for the difference in each case. We discuss the relationship of our models to actual tracer experiments and define physiological locations for our three compartments. Appearance of substrates is probably intermediate between our extreme cases. A numerical estimate of turnover for the substrate lactate in resting humans reveals an error bound of approximately 30%. We discuss sites of infusion and sampling consistent with our model, the effects of relaxing some of our modeling constraints, and experimental necessities for getting beyond the steady state.

First-pass Lung Uptake and Pulmonary Clearance of Propofol 

1999 ◽  
Vol 91 (6) ◽  
pp. 1780-1780 ◽  
Author(s):  
Jette A. Kuipers ◽  
Fred Boer ◽  
Wim Olieman ◽  
Anton G. L. Burm ◽  
James G. Bovill
Keyword(s):  
Pulmonary Tissue ◽  
Tissue Compartment ◽  
Arterial Blood ◽  
Concentration Time ◽  
Pulmonary Uptake ◽  
First Pass ◽  
Recirculatory Model ◽  
Pass Through ◽  
The Right ◽  
Kinetics Of

Background The principal site for elimination of propofol is the liver. The clearance of propofol exceeds hepatic blood flow; therefore, extrahepatic clearance is thought to contribute to its elimination. This study examined the pulmonary kinetics of propofol using part of an indocyanine green (ICG) recirculatory model. Methods Ten sheep, immobilized in a hammock, received injections of propofol (4 mg/kg) and ICG (25 mg) via two semipermanent catheters in the right internal jugular vein. Arterial blood samples were obtained from the carotid artery. The ICG injection was given for measurement of intravascular recirculatory parameters and determination of differences in propofol and ICG concentration-time profiles. No other medication was given during the experiment, and the sheep were not intubated. The arterial concentration-time curves of ICG were analyzed with a recirculatory model. The pulmonary uptake and elimination of propofol was analyzed with the central part of that model extended with a pulmonary tissue compartment allowing elimination from that compartment. Results During the experiment, cardiac output was 3.90+/-0.72 l/min (mean +/- SD). The blood volume in heart and lungs, measured with ICG, was 0.66+/-0.07 l. A pulmonary tissue compartment of 0.47+/-0.16 l was found for propofol. The pulmonary first-pass elimination of propofol was 1.14+/-0.23 l/min. Thirty percent of the dose was eliminated during the first pass through the lungs. Conclusions Recirculatory modeling of ICG allows modeling of the first-pass pulmonary kinetics of propofol concurrently. Propofol undergoes extensive uptake and first-pass elimination in the lungs.

scholarly journals [11C]mHED PET follows a two-tissue compartment model in mouse myocardium with norepinephrine transporter (NET)-dependent uptake, while [18F]LMI1195 uptake is NET-independent

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Linjing Mu ◽  
Stefanie D. Krämer ◽  
Geoffrey I. Warnock ◽  
Ahmed Haider ◽  
Susan Bengs ◽  
...  
Keyword(s):  
Kinetic Modelling ◽  
Compartment Model ◽  
Norepinephrine Transporter ◽  
Input Function ◽  
Experimental Models ◽  
Mouse Heart ◽  
Myocardial Uptake ◽  
Compartment Models ◽  
Tissue Compartment ◽  
Positron Emission

Abstract Purpose Clinical positron emission tomography (PET) imaging of the presynaptic norepinephrine transporter (NET) function provides valuable diagnostic information on sympathetic outflow and neuronal status. As data on the NET-targeting PET tracers [11C]meta-hydroxyephedrine ([11C]mHED) and [18F]LMI1195 ([18F]flubrobenguane) in murine experimental models are scarce or lacking, we performed a detailed characterization of their myocardial uptake pattern and investigated [11C]mHED uptake by kinetic modelling. Methods [11C]mHED and [18F]LMI1195 accumulation in the heart was studied by PET/CT in FVB/N mice. To test for specific uptake by NET, desipramine, a selective NET inhibitor, was administered by intraperitoneal injection. [11C]mHED kinetic modelling with input function from an arteriovenous shunt was performed in three mice. Results Both tracers accumulated in the mouse myocardium; however, only [11C]mHED uptake was significantly reduced by excess amount of desipramine. Myocardial [11C]mHED uptake was half-saturated at 88.3 nmol/kg of combined mHED and metaraminol residual. After [11C]mHED injection, a radiometabolite was detected in plasma and urine, but not in the myocardium. [11C]mHED kinetics followed serial two-tissue compartment models with desipramine-sensitive K1. Conclusion PET with [11C]mHED but not [18F]LMI1195 provides information on NET function in the mouse heart. [11C]mHED PET is dose-independent in the mouse myocardium at < 10 nmol/kg of combined mHED and metaraminol. [11C]mHED kinetics followed serial two-tissue compartment models with K1 representing NET transport. Myocardial [11C]mHED uptake obtained from PET images may be used to assess cardiac sympathetic integrity in mouse models of cardiovascular disease.

Case Report: When all claims that it is necrotizing fasciitis but Point of care ultrasound (POCUS) proves the opposite!

POCUS Journal ◽  
2018 ◽  
Vol 3 (1) ◽  
pp. 13-14
Author(s):  
Hadiel Kaiyasah, MD, MRCS (Glasgow), ABHS-GS ◽  
Maryam Al Ali, MBBS
Keyword(s):  
Emergency Department ◽  
Critical Care ◽  
Case Report ◽  
Soft Tissue ◽  
Necrotizing Fasciitis ◽  
Soft Tissue Infection ◽  
Critical Care Unit ◽  
Point Of Care ◽  
Point Of Care Ultrasound ◽  
Soft Tissue Infections

Soft tissue ultrasound (ST-USS) has been shown to be of utmost importance in assessing patients with soft tissue infections in the emergency department or critical care unit. It aids in guiding the management of soft tissue infection based on the sonographic findings.

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