Search

Introduction. Positron emission tomography (PET) is increasingly applied for infection imaging using [18F]FDG as tracer, but uptake is unspecific. The present study compares the kinetics of [18F]FDG and three other PET tracers with relevance for infection imaging. Methods. A juvenile porcine osteomyelitis model was used. Eleven pigs underwent PET/CT with 60-minute dynamic PET imaging of [18F]FDG, [68Ga]Ga-citrate, [11C]methionine, and/or [11C]donepezil, along with blood sampling. For infectious lesions, kinetic modelling with one- and two-tissue-compartment models was conducted for each tracer. Results. Irreversible uptake was found for [18F]FDG and [68Ga]Ga-citrate; reversible uptake was found for [11C]methionine (two-tissue model) and [11C]donepezil (one-tissue model). The uptake rate for [68Ga]Ga-citrate was slow and diffusion-limited. For the other tracers, the uptake rate was primarily determined by perfusion (flow-limited uptake).Net uptake rate for [18F]FDGand distribution volume for [11C]methionine were significantly higher for infectious lesions than for correspondingly noninfected tissue. For [11C]donepezil in pigs, labelled metabolite products appeared to be important for the analysis. Conclusions. The kinetics of the four studied tracers in infection was characterized. For clinical applications, [18F]FDG remains the first-choice PET tracer. [11C]methionine may have a potential for detecting soft tissue infections. [68Ga]Ga-citrate and [11C]donepezilwere not found useful for imaging of osteomyelitis. [ABSTRACT FROM AUTHOR]

Vascular adhesion protein 1 is a leukocyte homing-associated glycoprotein, which upon inflammation rapidly translocates from intracellular sources to the endothelial cell surface. It has been discovered that the cyclic peptide residues 283-297 of sialic acid-binding IgG-like lectin 9 (Siglec-9) 'CARLSLSWRGLTLCPSK' bind to vascular adhesion protein 1 and hence makes the radioactive analogues of this compound ([68Ga]Ga-DOTA-Siglec-9) interesting as a noninvasive visualizing marker of inflammation. Three different approaches to the radiosynthesis of [68Ga]Ga-DOTA-Siglec-9 are presented and compared with previously published methods. A simple, robust radiosynthesis of [68Ga]Ga-DOTA-Siglec-9 with a yield of 62% (non decay-corrected) was identified, and it had a radiochemical purity >98% and a specific radioactivity of 35 MBq/nmol. Furthermore, the protein binding and stability of [68Ga]Ga-DOTA-Siglec-9 were analyzed in vitro in mouse, rat, rabbit, pig, and human plasma and compared with in vivo pig results. The plasma in vitro protein binding of [68Ga]Ga-DOTA-Siglec-9 was the lowest in the pig followed by rabbit, human, rat, and mouse. It was considerably higher in the in vivo pig experiments. The in vivo stability in pigs was lower than the in vitro stability. Despite considerable species differences, the observed characteristics of [68Ga]Ga-DOTA-Siglec-9 are suitable as a positron emission tomography tracer. [ABSTRACT FROM AUTHOR]

Background: Osteomyelitis is a serious disease which can be difficult to treat despite properly instituted antibiotic therapy. This appears to be related at least partly to degraded vascularisation in the osteomyelitic (OM) lesions. Studies of perfusion in OM bones are, however, few and not quantitative. Quantitative assessment of perfusion could aid in the selection of therapy. A non-invasive, quantitative way to study perfusion is dynamic [O]water positron emission tomography (PET). We aim to demonstrate that the method can be used for measuring perfusion in OM lesions and hypothesize that perfusion will be less elevated in OM lesions than in soft tissue (ST) infection. The study comprised 11 juvenile pigs with haematogenous osteomyelitis induced by injection of Staphylococcus aureus into the right femoral artery 1 week before scanning (in one pig, 2 weeks). The pigs were dynamically PET scanned with [O]water to quantify blood perfusion. OM lesions ( N = 17) in long bones were studied, using the left limb as reference. ST lesions ( N = 8) were studied similarly. Results: Perfusion was quantitatively determined. Perfusion was elevated by a factor 1.5 in OM lesions and by a factor 6 in ST lesions. Conclusions: Blood perfusion was successfully determined in pathological subacute OM lesions; average perfusion was increased compared to that in a healthy bone, but as hypothesized, the increase was less than in ST lesions, indicating that the infected bone has less perfusion reserve than the infected soft tissue. [ABSTRACT FROM AUTHOR]

Several guidelines for bioelectrical impedance analysis (BIA) have been prepared for adults, but not for children. For that reason, there is a pressing need to develop a consensus set of guidelines to facilitate standardisation of BIA in this important group. This review provides an introduction to BIA, highlights critical factors that may impact on BIA and identifies areas where there is a need for further research in order to increase the quality of impedance measurements and prediction of body composition in children. Although the results of this review highlights a lack of studies in children to provide definitive BIA guidelines, the technique has, however, still proven valuable for body composition assessment in ill and healthy children. To fill the gaps in our knowledge, future studies should focus on methodological issues, particularly with regard to hydration, voiding, clothing, skin preparation and body position. The review may advantageously be used as a checklist in the planning of future studies. Finally, this review forms the basis for the development of guidelines for BIA assessment in this particular group; a task appropriately to be undertaken by scientific societies within the field. [ABSTRACT FROM PUBLISHER]

Background: Lu is used in peptide receptor radionuclide therapies for the treatment of neuroendocrine tumors. Based on the recent literature, SST2 antagonists are superior to agonists in tumor uptake. The compound OPS201 is the novel somatostatin antagonist showing the highest SST2 affinity. The aim of this study was to measure the in vivo biodistribution and dosimetry of Lu-OPS201 in five anesthetized Danish Landrace pigs as an appropriate substitute for humans to quantitatively assess the absorbed doses for future clinical applications. Results: Lu-OPS201 was obtained with a specific activity ranging from 10 to 17 MBq/μg. Prior to administration, the radiochemical purity was measured as s > 99.7 % in all cases. After injection, fast clearance of the compound from the blood stream was observed. Less than 5 % of the injected activity was presented in blood 10 min after injection. A series of SPECT/CT and whole-body scans conducted until 10 days after intravenous injection showed uptake mostly in the liver, spine, and kidneys. There was no visible uptake in the spleen. Blood samples were taken to determine the time-activity curve in the blood. Time-activity curves and time-integrated activity coefficients were calculated for the organs showing visible uptake. Based on these data, the absorbed organ dose coefficients for a 70-kg patient were calculated with OLINDA/EXM. For humans after an injection of 5 GBq Lu-OPS201, the highest predicted absorbed doses are obtained for the kidneys (13.7 Gy), the osteogenic cells (3.9 Gy), the urinary bladder wall (1.8 Gy), and the liver (1.0 Gy). No metabolites of Lu-OPS201 were found by radio HPLC analysis. None of the absorbed doses calculated will exceed organ toxicity levels. Conclusions: The Lu-OPS201 was well tolerated and caused no abnormal physiological or behavioral signs. In vivo distributions and absorbed doses of pigs are comparable to those observed in other publications. According to the biodistribution data in pigs, presented in this work, the expected radiation exposure in humans will be within the acceptable range. [ABSTRACT FROM AUTHOR]

Combined PET and SPECT scanning can give supplementary information. However, activity from PET radionuclides can cause background counts and increased dead time in [gamma] camera imaging (SPECT or planar) because the 511-keV photons can penetrate collimators designed for lower energies. This study investigated how to manage this issue, including what levels of PET radionuclides can be tolerated when a [gamma]-camera investigation is performed. METHODS: Different combinations of (68)Ga (PET radionuclide), (99m)Tc (low-energy radionuclide), and (111)In (medium-energy radionuclide) were scanned by a [gamma] camera. Standard low-, medium-, and high-energy collimators were used with the [gamma] camera. Dead time and counts near and distant from the sources were recorded. RESULTS: Down scatter from 511 keV can give rise to a considerable number of counts within the (99m)Tc or (111)In energy windows, especially when the PET source is close to the camera head. Over the full camera head, the PET source can result in more counts per megabecquerel than the SPECT source ((99m)Tc or (111)In). Counts from the PET source were distributed over a large region of the camera head. With medium- and high-energy collimators, the sensitivity to the PET radionuclide was found to be about 10% of the sensitivity to (99m)Tc and about 20% of the sensitivity to (111)In, as measured within a 3-cm-radius region of interest. CONCLUSION: If PET radionuclides of activity 1 MBq or higher are present in the patient at the time of SPECT, a medium-energy collimator should be used. Counts from PET sources will in SPECT usually be seen as a diffuse background rather than as foci. The thick septa of high-energy collimators may result in structure in the image, and a high-energy collimator is recommended only if PET activity is greater than 10 MBq. [ABSTRACT FROM AUTHOR]

Combined PET and SPECT scanning can give supplementary information. However, activity from PET radionuclides can cause background counts and increased dead time in camera g imaging (SPECT or planar) because the 511-keV photons can penetrate collimators designed for lower energies. This study investigated how to manage this issue, including what levels of PET radionuclides can be tolerated when γ-camera investigation is performed. Methods: Different combinations of 68Ga (PET radionuclide), 99mTc (low-energy radionuclide), and 111In (medium-energy radionuclide) were scanned by γ camera. Standard low-, medium-, and high-energy collimators were used with the γ camera. Dead time and counts near and distant from the sources were recorded. Results: Down scatter from 511 keV can give rise to a considerable number of counts within the 99mTc or 111In energy windows, especially when the PET source is close to the camera head. Over the full camera head, the PET source can result in more counts per megabecquerel than the SPECT source (99mTc or 111In). Counts from the PET source were distributed over a large region of the camera head. With medium- and high-energy collimators, the sensitivity to the PET radionuclide was found to be about 10% of the sensitivity to 99mTc and about 20% of the sensitivity to 111In, as measured within a 3-cm-radius region of interest. Conclusion: If PET radionuclides of activity 1 MBq or higher are present in the patient at the time of SPECT, a medium-energy collimator should be used. Counts from PET sources will in SPECT usually be seen as a diffuse background rather than as foci. The thick septa of high-energy collimators may result in structure in the image, and a high-energy collimator is recommended only if PET activity is greater than 10 MBq. [ABSTRACT FROM AUTHOR]

Background . The one-pool or slope-intercept technique is widely used when determining total 51Cr-EDTA plasma clearance (Cl). The one-pool clearance (Cl 1), which always exceeds Cl, has mostly been corrected to Cl by multiplication by a constant factor = 0.80, suggested by Chantler (CH0.80), or by using a second-order polynomial originally proposed by Brøchner-Mortensen (BM) and later recommended by the British Nuclear Medicine Society (BMBNMS). Theoretical considerations indicate that the CH correction gives a systematic overestimate of Cl, whereas the BM correction may underestimate Cl at high values. Objective . To assess the accuracy of Cl as estimated from Cl 1 corrected either by CH0.80 or by second-order polynomials. Material and methods . Clref was determined in 149 subjects (M/F/children: 71/46/32) from a complete plasma curve followed for 4-5 h after injection of 51Cr-EDTA (range of Clref : 8-183 mL/min/1.73 m2). Clest was determined from Cl 1 subsequently corrected by CH0.80 and four second-order polynomials. Results . Using CH0.80 correction, Clest underestimated Clref (by a maximum of 20 %) at Clref values less than about 100 mL/min/1.73 m2 in children and 130 mL/min/1.73 m2 in adults. At higher clearance levels, Clref was increasingly overestimated. Taking the BMBNMS correction as representative of second-order polynomials, Clest increasingly underestimated Clref at high levels, the error being 10 % at a Clref value of about 175 mL/min/1.73 m2. Conclusions. We suggest that the tested correction equations are replaced by the given common correction equation based on the “true” relationship between Cl 1 and Cl thoroughly described in part I of this study. [ABSTRACT FROM AUTHOR]

Background: [ 68 Ga]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 [ 68 Ga]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 [ 68 Ga]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 [ 68 Ga]Ga-DOTA-Siglec-9 uptake in porcine soft tissue infections are best described by the 2-tissue compartment model.

Background: Accumulation of extracellular water (ECW) is a major clinical manifestation of nephrotic syndrome (NS) in children. Bioimpedance spectroscopy (BIS) is a simple, noninvasive technique that reflects body water volumes. BIS can further measure cell membrane capacitance (C M ), which may be altered in NS. The aims of the study were to explore how BIS measurements could reflect disease status in NS, while avoiding prediction equations which are often only validated in adult populations., Methods: The study involved 8 children (2-10 years) with active NS (ANS group), 5 of which were also studied at NS remission (NSR group), as well as 38 healthy children of similar age (HC group). BIS measurements determined resistances R INF , R E , and R I (reflecting total body water, extracellular water, and intracellular water) and C M . Also resistance indices based on height (H) were considered, RI = H 2 /R., Results: It was found that R E and R INF were significantly lower in the ANS group than in both NSR and HC groups (p < 0.001). Corresponding resistance indices were significantly higher in the ANS group than in the NSR (p < 0.01) and the HC (p < 0.05) groups, in accordance with elevated water volumes in NS patients. Indices of intracellular water were not significantly different between groups. C M was significantly lower in the ANS group than in NSR and HC groups (p < 0.05)., Conclusion: BIS could distinguish children with active NS from well-treated and healthy children. Studies with more children are warranted.

Background: In GFR measurements with radiotracers, there is evidence that a two-compartment model is unable to describe the full plasma curve, including early time points, but analyses generally focus on two-compartment models., Aims: To analyze both the mammillary and catenary three-compartment model and to determine empirical relations between model constants and the overall GFR and ECV (extra-cellular volume)., Material and Methods: Mathematical analysis of the three-compartment model. Full-curve patient data from 32 adults and 7 children were used to relate model parameters to GFR and ECV., Results: Model volumes were found to be roughly proportional to ECV. In both models, the central (plasma) volume was V1 = 0.24 × ECV and elimination rate from V1 was k10 = 4.2 × GFR/ECV. In the mammillary model, the two parallel volumes were V2 = 0.28 × ECV, V3 = 0.48 × ECV, and intercompartmental clearances were Cl12 [mL/min] = 0.0058 × ECV [mL], Cl13 = 0.042 × ECV. In the catenary model, the serial volumes were V2 = 0.60 × ECV, V3 = 0.16 × ECV, with clearances Cl12 = 0.048 × ECV, Cl23 = 0.0036 × ECV., Conclusion: Insight into the three-compartment model was achieved, and empirical relations to ECV and GFR/ECV were determined.

Introduction: Positron emission tomography (PET) is increasingly applied for infection imaging using [ 18 F]FDG as tracer, but uptake is unspecific. The present study compares the kinetics of [ 18 F]FDG and three other PET tracers with relevance for infection imaging., Methods: A juvenile porcine osteomyelitis model was used. Eleven pigs underwent PET/CT with 60-minute dynamic PET imaging of [ 18 F]FDG, [ 68 Ga]Ga-citrate, [ 11 C]methionine, and/or [ 11 C]donepezil, along with blood sampling. For infectious lesions, kinetic modelling with one- and two-tissue-compartment models was conducted for each tracer., Results: Irreversible uptake was found for [ 18 F]FDG and [ 68 Ga]Ga-citrate; reversible uptake was found for [ 11 C]methionine (two-tissue model) and [ 11 C]donepezil (one-tissue model). The uptake rate for [ 68 Ga]Ga-citrate was slow and diffusion-limited. For the other tracers, the uptake rate was primarily determined by perfusion (flow-limited uptake). Net uptake rate for [ 18 F]FDG and distribution volume for [ 11 C]methionine were significantly higher for infectious lesions than for correspondingly noninfected tissue. For [ 11 C]donepezil in pigs, labelled metabolite products appeared to be important for the analysis., Conclusions: The kinetics of the four studied tracers in infection was characterized. For clinical applications, [ 18 F]FDG remains the first-choice PET tracer. [ 11 C]methionine may have a potential for detecting soft tissue infections. [ 68 Ga]Ga-citrate and [ 11 C]donepezil were not found useful for imaging of osteomyelitis.