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First-order compartment models are common tools for modelling many biological processes, including pharmacokinetics. Given the compartments and the transfer rates, solutions for the time-dependent quantity (or concentration) curves can normally be described by a sum of exponentials. This paper investigates cases that go beyond simple sums of exponentials. With specific relations between the transfer rate constants, two exponential rate constants can be equal, in which case the normal solution cannot be used. The conditions for this to occur are discussed, and advice is provided on how to circumvent these cases. An example of an analytic solution is given for the rare case where an exact equality is the expected result. Furthermore, for models with at least three compartments, cases exist where the solution to a real-valued model involves complex-valued exponential rate constants. This leads to solutions with an oscillatory element in the solution for the tracer concentration, i.e., there are cases where the solution is not a simple sum of (real-valued) exponentials but also includes sine and cosine functions. Detailed solutions for three-compartment cases are given. As a tentative conclusion of the analysis, oscillatory solutions appear to be tied to cases with a cyclic element in the model itself., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Kidney surgery often includes organ ischaemia with a risk of acute kidney injury. The present study tested if treatment with the combined angiotensin II-angiotensin II receptor type 1 and neprilysin blocker Entresto (LCZ696, sacubitril/valsartan) protects filtration barrier and kidney function after ischaemia and partial nephrectomy (PN) in pigs. Single kidney glomerular filtration rate (GFR) by technetium-99m diethylene-triamine-pentaacetate clearance was validated (n = 6). Next, four groups of pigs were followed for 15 days (n = 24) after PN (one-third right kidney, 60 min ischaemia) + Entresto (49/51 mg/day; n = 8), PN + vehicle (n = 8), sham + Entresto (49/51 mg/day; n = 4) and sham + vehicle (n = 4). GFR, diuresis and urinary albumin were measured at baseline and from each kidney after 15 days. The sum of single-kidney GFR (right 25 ± 6 mL/min, left 31 ± 7 mL/min) accounted for the total GFR (56 ± 14 mL/min). Entresto had no effect on baseline blood pressure, p-creatinine, mid-regional pro-atrial natriuretic peptide (MR-proANP), heart rate and diuresis. After 15 days, Entresto increased GFR in the uninjured kidney (+23 ± 6 mL/min, P < .05) and reduced albuminuria from both kidneys. In the sham group, plasma MR-proANP was not altered by Entresto; it increased to similar levels 2 h after surgery with and without Entresto. Fractional sodium excretion increased with Entresto. Kidney histology and kidney injury molecule-1 in cortex tissue were not different. In conclusion, Entresto protects the filtration barrier and increases the functional adaptive response of the uninjured kidney., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Subcutaneous (SC) hydration is a valuable method for treating dehydration in the very old patients. Data are absent on the absorption rate, and the availability of SC infused fluid in the circulation in this group of patients where SC hydration is particularly relevant., Methods: We performed an explorative study on ill very old (range 78-84 years old) geriatric patients with comorbidities who received an SC infusion of 235 ml isotonic saline containing a technetium-99m pertechnetate tracer. The activity over the infusion site was measured using a gamma detector to assess the absorption rate from the SC space. The activity was measured initially every 5 minutes, with intervals extended gradually to 15 minutes. Activity in blood samples and the thyroid gland was measured to determine the rate of availability in the circulation., Results: Six patients were included. The mean age was 81 years (SD 2.1), the number of comorbidities was 4.6 (SD 1.3), and the Tilburg frailty indicator was 3.8 (SD 2.4). When the infusion was completed after 60 minutes, 53% (95% CI 50-56%) of the infused fluid was absorbed from the SC space, with 88% (95% CI 86-90%) absorbed one hour later. The absorption rate from the SC space right after the completion of the infusion was 127 ml/h (95% CI 90-164 ml/h). The appearance of the fluid into the blood and the thyroid gland verified the transfer from SC to circulation., Conclusion: This first explorative study of absorption of SC infused fluid in the very old found an acceptable amount of fluid absorbed from the SC space into the circulation one hour after infusion had ended. Results are uniform but should be interpreted cautiously due to the low sample size., Trial Registration: ClinicalTrials.gov Identifier: NCT04536324., Competing Interests: The authors have declared that no competing interests exist.

Background: [ 18 F]FDG and [ 11 C]methionine accumulate in lymph nodes draining S. aureus -infected foci. The lymph nodes were characterized by weight, [ 11 C]methionine- and [ 18 F]FDG-positron emissions tomography (PET)/computed tomography (CT), and immunohistochemical (IHC)-staining., Methods: 20 pigs inoculated with S. aureus into the right femoral artery were PET/CT-scanned with [ 18 F]FDG, and nine of the pigs were additionally scanned with [ 11 C]methionine. Mammary, medial iliac, and popliteal lymph nodes from the left and right hind limbs were weighed. IHC-staining for calculations of area fractions of Ki-67, L1, and IL-8 positive cells was done in mammary and popliteal lymph nodes from the nine pigs., Results: The pigs developed one to six osteomyelitis foci. Some pigs developed contiguous infections of peri-osseous tissue and inoculation-site abscesses. Weights of mammary and medial iliac lymph nodes and their [ 18 F]FDG maximum Standardized Uptake Values (SUV FDGmax ) showed a significant increase in the inoculated limb compared to the left limb. Popliteal lymph node weight and their FDG uptake did not differ significantly between hind limbs. Area fractions of Ki-67 and IL-8 in the right mammary lymph nodes and SUV Metmax in the right popliteal lymph nodes were significantly increased compared with the left side., Conclusion: The PET-tracers [ 18 F]FDG and [ 11 C]methionine, and the IHC- markers Ki-67 and IL-8, but not L1, showed increased values in lymph nodes draining soft tissues infected with S. aureus . The increase in [ 11 C]methionine may indicate a more acute lymph node response, whereas an increase in [ 18 F]FDG may indicate a more chronic response.

The development of new and better radioactive tracers capable of detecting and characterizing osteomyelitis is an ongoing process, mainly because available tracers lack selectivity towards osteomyelitis. An integrated part of developing new tracers is the performance of in vivo tests using appropriate animal models. The available animal models for osteomyelitis are also far from ideal. Therefore, developing improved animal osteomyelitis models is as important as developing new radioactive tracers. We recently published a review on radioactive tracers. In this review, we only present and discuss osteomyelitis models. Three ethical aspects (3R) are essential when exposing experimental animals to infections. Thus, we should perform experiments in vitro rather than in vivo (Replacement), use as few animals as possible (Reduction), and impose as little pain on the animal as possible (Refinement). The gain for humans should by far exceed the disadvantages for the individual experimental animal. To this end, the translational value of animal experiments is crucial. We therefore need a robust and well-characterized animal model to evaluate new osteomyelitis tracers to be sure that unpredicted variation in the animal model does not lead to a misinterpretation of the tracer behavior. In this review, we focus on how the development of radioactive tracers relies heavily on the selection of a reliable animal model, and we base the discussions on our own experience with a porcine model.

Introduction: Radiotracers are widely used in medical imaging, using techniques of gamma-camera imaging (scintigraphy and SPECT) or positron emission tomography (PET). In bone marrow infection, there is no single routine test available that can detect infection with sufficiently high diagnostic accuracy. Here, we review radiotracers used for imaging of bone marrow infection, also known as osteomyelitis, with a focus on why these molecules are relevant for the task, based on their physiological uptake mechanisms. The review comprises [ 67 Ga]Ga-citrate, radiolabelled leukocytes, radiolabelled nanocolloids (bone marrow) and radiolabelled phosphonates (bone structure), and [ 18 F]FDG as established radiotracers for bone marrow infection imaging. Tracers that are under development or testing for this purpose include [ 68 Ga]Ga-citrate, [ 18 F]FDG, [ 18 F]FDS and other non-glucose sugar analogues, [ 15 O]water, [ 11 C]methionine, [ 11 C]donepezil, [ 99m Tc]Tc-IL-8, [ 68 Ga]Ga-Siglec-9, phage-display selected peptides, and the antimicrobial peptide [ 99m Tc]Tc-UBI 29-41 or [ 68 Ga]Ga-NOTA-UBI 29-41 ., Conclusion: Molecular radiotracers allow studies of physiological processes such as infection. None of the reviewed molecules are ideal for the imaging of infections, whether bone marrow or otherwise, but each can give information about a separate aspect such as physiology or biochemistry. Knowledge of uptake mechanisms, pitfalls, and challenges is useful in both the use and development of medically relevant radioactive tracers.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.vascn.2019.106648. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal., (Copyright © 2019. Published by Elsevier Inc.)

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.

Both 99m Tc-DTPA and 51 Cr-EDTA are widely used to determine glomerular filtration rate (GFR), but few direct comparative studies exist. The shortage of 51 Cr-EDTA makes a direct comparison highly relevant. The aim of the study was to investigate if there is any clinically relevant difference between plasma clearance of 99m Tc-DTPA and 51 Cr-EDTA. Patients ≥18 years of age referred for routine GFR measurement by 51 Cr-EDTA were prospectively enrolled. The two tracers (10 MBq 99m Tc-DTPA (CaNa 3 -DTPA) and 2.5 MBq 51 Cr-EDTA) were intravenously injected at time zero. A standard 4-sample technique was applied with samples collected at 180, 200, 220 and 240 min, if the estimated GFR (eGFR) was ≥30 mL/min. A comparison of single-sample GFR based on the 200 min sample was also conducted. Fifty-six patients were enrolled in the study. All patients had an estimated GFR >30 mL/min/1.73 m 2 . No patients suffered from ascites or significant oedema. The mean 51 Cr-EDTA plasma clearance was 82 mL/min (range 16-226). The plasma clearances determined by the two methods were highly correlated ( r  = 0.993). The plasma clearance was significantly higher when measured by 99m Tc-DTPA than by 51 Cr-EDTA ( p  = 0.01), but the numerical difference was minimal (mean difference 1.4 mL/min; 95% limits of agreement (LOA) -6.6 to 9.4). The difference between the two methods was independent of the level of renal function. Similar results were found for one-sample GFR. No clinically relevant differences were found between the plasma clearance of 99m Tc-DTPA and that of 51 Cr-EDTA. Therefore, 99m Tc-DTPA can replace 51 Cr-EDTA when needed.

Although compartment models are frequently used in pharmacokinetics, it is difficult to find complete analytical formulas describing the behaviour of drugs in universal simpler compartment models in the accessible literature. The paper presents derivations of formulas for general two- and three-compartment models, including the possibilities of original non-zero quantity in all compartments and elimination from all compartments. Formulas for four-compartment models are also derived with the restriction that original quantity is non-zero in only one compartment. Derivation uses Laplace transformation but does not require prior knowledge of the technique. The derived analytical formulas are verified numerically. These formulas can be easily simplified to less complex cases., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Oedema, characterized by accumulation of extracellular water (ECW), is one of the major clinical manifestations in children suffering from nephrotic syndrome (NS). The lack of a simple, inexpensive and harmless method for assessing ECW may be solved by the use of the bioelectrical impedance analysis (BIA) technique. The aims of this study were to examine whether phase angle (PA), bioelectrical impedance vector analysis (BIVA) and the impedance ratio (IR) reflect change in disease status in children with NS., Methods: Eight children (age range: 2-10 years) with active NS (ANS group) were enrolled. In five of these (ANS* subgroup), impedance was also measured at remission (NSR group). Thirty-eight healthy children (age range: 2-10 years) were included as healthy controls (HC group). Whole-body impedance was measured with a bioimpedance spectroscopy device (Xitron 4200) with surface electrodes placed on the wrist and ankle., Results: Values of PA, BIVA and IR were found to be significantly lower (p-value range < 0.001 to < 0.01) in the ANS patients compared to the HC and NSR groups. No significant differences were observed between the NSR and HC groups., Conclusion: The studied parameters can be used to assess change in disease status in NS patients. Data were consistent with NS being associated with expansion of ECW.

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.

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 [ 15 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 [ 15 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.

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.

Background: Bioelectrical impedance analysis (BIA) requires a high degree of standardisation in order to ensure valid and reproducible impedance measurements. The overall aim of this review was to study the degree to which BIA papers conducted in healthy paediatric populations (aged 0-17 years) were standardised., Methods: Literature was identified on the basis of a systematic search of internationally-recognised electronic databases and hand searching of the reference lists of the included papers in order to identify additional relevant papers. The review was limited to lead-type BIA devices for whole-body, segmental- and focal impedance measurements. In total, 71 papers published between 1988 and 2016 were included. To evaluate the degree of standardisation of the papers, a recently published review detailing critical factors that may impact on BIA measurements in children was used as a model for structuring and extracting data., Results: There was a general lack of BIA standardisation, or its reporting, in the papers under review, which hinders comparison of data between studies and could potentially lead to erroneous measurements., Conclusions: If the BIA technique should be accepted clinically for routine use in paediatric populations, there is a need for an increased focus on the importance of improved standardisation and its reporting in future studies. Consequently, this review contains recommendations for performing and reporting BIA measurements in a standardised manner.

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 ([ 68 Ga]Ga-DOTA-Siglec-9) interesting as a noninvasive visualizing marker of inflammation. Three different approaches to the radiosynthesis of [ 68 Ga]Ga-DOTA-Siglec-9 are presented and compared with previously published methods. A simple, robust radiosynthesis of [ 68 Ga]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 [ 68 Ga]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 [ 68 Ga]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 [ 68 Ga]Ga-DOTA-Siglec-9 are suitable as a positron emission tomography tracer., (Copyright © 2017 John Wiley & Sons, Ltd.)

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.

Background: (177)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 (177)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: (177)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 (177)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 (177)Lu-OPS201 were found by radio HPLC analysis. None of the absorbed doses calculated will exceed organ toxicity levels., Conclusions: The (177)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.

Introduction: An important issue in multitracer studies is the separation of signals from the different radiotracers. This is especially the case when an early tracer has a long physical half-life and kinetic modelling has to be performed, because the early tracer can confer a long-lived contaminating background not only to images but also to a measured input function derived from blood samples. In this study, we examined data from a sequential multitracer infection study involving In (t1/2=2.8 days), investigating the influence on gamma counting of blood samples and on the kinetic modelling of subsequent PET tracers. Blood sample counts were corrected by recounting the samples a few days later. A more optimal choice of energy window was also explored. The effect of correction versus noncorrection was investigated using a two-tissue kinetic model with irreversible uptake (K1, k2, k3)., Results: K1 was least affected and k3 was most affected by the contamination, corresponding to the effect being relatively larger on the late part of the blood input function. A narrower energy window reduced the problem, but this will not be possible for all types of contaminating background., Conclusion: Gamma counting of blood samples can lead to a contaminating background not observed in PET imaging and this background can affect kinetic modelling. If the contaminating tracer has a much longer half-life than the foreground tracer, then the problem can be solved by late recounting of the samples.

Purpose of the Report: When thyroid scintigraphy (TS) is performed after contrast-enhanced CT (CE-CT), tracer uptake of 99mTcO4 in the thyroid gland can be inhibited by free iodide. Currently, it is recommended to postpone TS until 4 to 8 weeks after CE-CT, but few data exist to support this recommendation. The purpose was to investigate the effect of CE-CT and other variables for the diagnostic quality of TS., Patients and Methods: This retrospective study included 196 patients subjected to TS less than 3 months after a CE-CT (median, 66 days). Patients with elevated thyroid-stimulating hormone (>4.5 mIU/L) or suspected thyroiditis were excluded. Logistic regression was used to calculate the probability of a TS of diagnostic quality with the variables days since CE-CT, age, thyroid-stimulating hormone, and kidney function (eGFR)., Results: Days since CT and age were highly significant (P < 0.001) predictors for diagnostic TS. The probability of diagnostic quality TS after CE-CT increased with time and reached approximately 70% to 80% 6 to 8 weeks after CE-CT. Analysis of age-specific populations showed age to be a strong independent factor., Conclusions: Our findings are in consensus with the currently recommended interval of 6 to 8 weeks between CE-CT and TS. However, our results indicate that patient age should be taken into account, and we suggest the following delay from CE-CT to TS: 4 weeks for patients aged younger than 50 years, 6 weeks for patients aged 50 to 60 years, and 8 weeks for patients aged older than 60 years.

Unlabelled: Combined PET and SPECT scanning can give supplementary information. However, activity from PET radionuclides can cause background counts and increased dead time in γ 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 γ-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 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 (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.

Background: The aim of this study was to compare the ability of renal indicators [serum creatinine (SCr), cystatin C (SCysC)] and glomerular filtration rate (GFR)-models to discriminate normal and reduced renal function. As a single cut-off level will always lead to false classifications, we propose using two cut-off levels, dividing renal function into normal or reduced, with an intermediate "gray zone" of indeterminable results., Methods: Glomerular filtration rate was measured by plasma clearance of (51)Cr-EDTA (13.7-147.4 mL/min/1.73 m(2)) in 119 children (age range 2.3-14.9 years). Reduced renal function was defined as a GFR of  <82 mL/min/1.73 m(2). SCr, SCysC, age-normalized creatinine (SCr-ratio), and eight published GFR-models were compared for their ability to correctly classify renal function as normal or reduced. Cut-off levels were determined so as to give 99 % certainty outside the gray zone., Results: The multivariable GFR-models by Schwartz et al. (J Am Soc Nephrol 2009; 20:629-637) and Zappitelli et al. (Am J Kidney Dis 2006; 48:221-230) and two models by Andersen et al. [Am J Kidney Dis 2012; 59(1):50-57: body cell mass (BCM)-model and Weight-model] performed significantly better than all other variables (P < 0.01), with the BCM-model performing the best (P < 0.05). The SCr-based Schwartz formula and SCr-ratio both performed better than SCr and SCysC., Conclusions: Among the 119 children enrolled in this study and the renal indicators tested, the BCM-model had the best diagnostic performance in terms of screening for normal or reduced renal function, and the SCr-ratio was a superior diagnostic tool to both SCr and SCysC.

Background: Instead of scaling glomerular filtration rate (GFR) to a body surface area of 1.73 m(2), it has been suggested to scale GFR to extracellular fluid volume (ECV). The ratio GFR/ECV has physiological meaning in that it indicates how often 'that which is to be regulated' (i.e. ECV) comes into contact with the 'regulator' (i.e. the kidneys)., Aim: The aim of the present study was as follows: to analyse two published calculation methods for determining ECV and GFR/ECV; to develop a new simple and accurate formula for determining ECV; and to compare and evaluate these methods., Materials and Methods: GFR was determined as (51)Cr-EDTA clearance. The study comprised 128 individuals (35 women, 66 men and 27 children) with a full (51)Cr-EDTA plasma concentration curve, determined from injection until 4-5 h p.i. Reference values for GFR and ECV were calculated from the full curve. One-pool approximations C/(1) and V(1) were calculated using only the final-slope curve. Four calculation methods were compared: simple one-pool values; GFR/ECV according to Peters and colleagues; ECV according to Brøchner-Mortensen (BM); and ECV according to a new method (JBM): y=2x-1, where x=Cl(1)/Cl and y=V(1)/ECV., Results: The new JBM method is accurate and can be explained theoretically. BM has a slight bias for high renal function. The Peters method had bias in our data. GFR/ECV had better precision than ECV alone, especially for BM and JBM, which were within -4% to +7% of the reference values (95% limits of agreement in adults)., Conclusion: GFR/ECV can be precisely determined, especially with the BM and JBM methods. Expressing GFR/ECV in unit %/h gives a simple interpretation. Normal ranges for GFR/ECV need to be established.

Background: Aiming to develop a more accurate cystatin C-based model for estimation of glomerular filtration rate (GFR) in children, we hypothesized that inclusion of body cell mass (BCM) would increase the accuracy of the GFR estimate in comparison to a well-established GFR reference method., Study Design: Diagnostic test accuracy study., Settings & Participants: 119 children (mean age, 8.8; range, 2.3-14.9 years) referred for GFR measurement by chromium 51 ethylenediaminetetraacetic acid ((51)Cr-EDTA) clearance (mean GFR, 98; range, 13.7-147.4 mL/min/1.73 m(2))., Index Test: GFR estimations by the 2 prediction models resulting from theoretical considerations corroborated by forward stepwise variable selection: GFR (mL/min) = 0.542 × (BCM/SCysC)(0.40) × (height × BSA/SCr)(0.65) and GFR (mL/min) = 0.426 × (weight/SCysC)(0.39) × (height × BSA/SCr)(0.64), where SCysC is serum cystatin C level, BSA is body surface area, and SCr is serum creatinine level. The accuracy and precision of these models were compared with 7 previously published prediction models using random subsampling cross-validation. Local constants and coefficients were calculated for all models. Root mean square error, R(2), and percentage of predictions within ±10% and ±30% of the reference GFR were calculated for all models. Based on 1,000 runs of the cross-validation procedure, median values and 2.5th and 97.5th quantiles of the validation parameters were calculated., Reference Test: GFR measurement by (51)Cr-EDTA clearance., Results: The BCM model predicted 98% within ±30% of reference GFR and 66% within ±10%, which was higher than for any other model. The weight model predicted 97.5% within ±30% of reference GFR and 62% within ±10%. The BCM model had the highest R(2) and the smallest root mean square error., Limitations: Included only 9 children with GFR <60 mL/min/1.73 m(2). Lack of independent validation cohort., Conclusions: The novel BCM model predicts GFR with higher accuracy than previously published models. The weight model is almost as accurate as the BCM model and allows for GFR estimation without knowledge of BCM. However, endogenous methods are still not sufficiently accurate to replace exogenous markers when GFR must be determined with high accuracy., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Bioimpedance spectroscopy (BIS) offers the possibility to perform rapid estimates of fluid distribution and body composition. Few studies, however, have addressed the precision and biological variation in a pediatric population. Our objectives were to evaluate precision, variation within- and between-days for the BIS-determined parameters total body fluid, extra-cellular fluid, intra-cellular fluid, body cell mass, fat-free mass, extra-cellular resistance, intra-cellular resistance and percentage body fat using a Xitron 4200., Methods: All 133 children (81 boys, 52 girls; 2.4-14.9 years) had one series measured on day one (precision population). Forty-four children had a second series on day one (within-day sub-population). Thirty-two children had a series measured on the next day (between-day sub-population). Each measurement series consisted of three repeated measurements. A linear mixed model was used for statistical analysis., Results: The precision was 0.3-0.8% in children ≥6 years and 0.5-2.4% in children <6 years with a statistically significant difference between the two age-groups (p<0.001). Within-day variation was 1.1-2.8% and between-day variation 2.4-5.7%. Total variation and reference change values are reported., Conclusion: The Xitron 4200 has a very good but age-dependent precision. The median value of three repeated measurements is recommended in order to avoid incorrect measurements., (Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Beta emitters, such as (90)Y, are increasingly being used for cancer treatment. However, beta emitters demand other precautions than gamma emitters during preparation and administration, especially concerning shielding., Aim: To discuss practical precautions for handling beta emitters in general, and specifically determine proper shielding for (90)Y, while comparing to (177)Lu and (131)I. The aim is achieved through the application of physical principles combined with results from practical experience., Material and Methods: Typical and maximal electron ranges were calculated for (131)I, (177)Lu, and (90)Y, using data from a freely available database. Bremsstrahlung yields were calculated for (90)Y shielded by lead, aluminium, or perspex. Bremsstrahlung spectrum from (90)Y shielded by perspex was measured, and attenuation of spectrum by lead was calculated. Whole-body and finger doses to persons preparing (90)Y-Zevalin were measured., Conclusions: Good laboratory practice is important to keep radiation doses low. To reduce bremsstrahlung, (90)Y should not be shielded by lead but instead perspex (10 mm) or aluminium (5 mm). Bremsstrahlung radiation can be further reduced by adding a millimetre of lead on the outside of the primary shielding material. If suitable shielding is used and larger numbers of handlings are divided among several persons, then handling of beta emitters can be a safe procedure.

Background: Total plasma clearance of (51)Cr-EDTA, Cl, is widely used as a measure of GFR. Commonly, only the final part of the plasma concentration curve is measured, and a one-pool clearance (slope-intercept clearance), Cl(1), is computed. Empirically determined second-order polynomials of the general form Cl = b x Cl(1) + c x Cl(1)(2) are usually used to estimate Cl from a measured Cl(1). However, theoretical considerations indicate that such corrections underestimate Cl at high values., Aims: To derive an analytically correct relationship between Cl and Cl(1) and determine the parameters involved for children and adults., Material and Methods: Cl was determined in 149 subjects (M/F/children: 71/46/32) from a complete plasma concentration curve followed for 4-5 h after injection of (51)Cr-EDTA (range of clearance: 8-183 mL/min/1.73 m(2)). Plasma volume, PV and the "missing" area under the plasma fraction curve, a (minutes), not used for determination of Cl(1), were measured., Results: The true relationship between Cl and Cl(1) is given by Cl = Cl(1)/(1 + f x Cl(1)), where f = a/PV. For men, women and children alike, the equation f = 0.0032 x BSA(-1.3) was applicable (BSA = body surface area in m(2)). Estimation errors on clearance were within +/-8% for adults and +/-13% for children (95% limits of agreement)., Conclusions: The true relationship between Cl and Cl(1) of (51)Cr-EDTA is given, resulting in a common correction equation applicable for children and adults. The new equation has better mathematical behaviour than quadratic equations on very high values of clearance and takes into account dependence on body size.

Background: The one-pool or slope-intercept technique is widely used when determining total (51)Cr-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 (CH(0.80)), or by using a second-order polynomial originally proposed by Brøchner-Mortensen (BM) and later recommended by the British Nuclear Medicine Society (BM(BNMS)). 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 CH(0.80) or by second-order polynomials., Material and Methods: Cl(ref) was determined in 149 subjects (M/F/children: 71/46/32) from a complete plasma curve followed for 4-5 h after injection of (51)Cr-EDTA (range of Cl(ref) : 8-183 mL/min/1.73 m(2)). Cl(est) was determined from Cl(1) subsequently corrected by CH(0.80) and four second-order polynomials., Results: Using CH(0.80) correction, Cl(est) underestimated Cl(ref) (by a maximum of 20%) at Cl(ref) values less than about 100 mL/min/1.73 m(2) in children and 130 mL/min/1.73 m(2) in adults. At higher clearance levels, Cl(ref) was increasingly overestimated. Taking the BM(BNMS) correction as representative of second-order polynomials, Cl(est) increasingly underestimated Cl(ref) at high levels, the error being 10% at a Cl(ref) value of about 175 mL/min/1.73 m(2)., 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.