Imaging infection and inflammation in veterinary practice.
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Animals↗
Biomedical subjects
A M Peters
Publications and source records attributed to A M Peters.
Inflammatory arthritis: imaging of endothelial cell activation with an indium-111-labeled F(ab')2 fragment of anti-E-selectin monoclonal antibody.
PURPOSE: To use imaging performed with an indium-111-labeled F(ab')2 fragment of monoclonal antibody that recognizes E-selectin (1.2B6) to evaluate inflammation. MATERIALS AND METHODS: After the in vivo immunoreactivity of In-111-F(ab')2 was verified, imaging experiments were conducted on pigs with induced arthritis of the right knee. In-111-labeled 1.2B6-F(ab')2, technetium-99m-hexamethylpropyleneamine oxime-labeled polymorphonuclear leukocytes (PMNs), and iodine-125-MOPC 21-labeled F(ab')2 (the control) were administered by means of intravenous injection. Scintigrams were obtained until 20 hours after injection, and tissue sampling was performed. RESULTS: Scintigrams showed uptake of 1.2B6 in the right knee but only faint filling of the joint space with PMNs. The right knee-to-left knee ratios on images obtained 20 hours after injection of the tracers were 10.8 +/- 3.6 for 1.2B6 and 1.1 +/- 0.4 for PMNs (P < .05). CONCLUSION: Endothelial cell immunotargeting with a radiolabeled anti-E-selectin F(ab')2 monoclonal antibody is feasible for use in imaging of inflammation.
Animals↗
Measurement of the pulmonary vascular granulocyte pool.
We have developed a technique for measuring the pulmonary granulocyte pool (PGP) as a fraction of the whole body total blood granulocyte pool (TBGP). The technique "captures" a dose of 99mTc-labeled granulocytes in a region of interest (ROI) over the lung during first pass by integrating an input time-activity curve from an ROI over the pulmonary artery, superior vena cava, or right ventricle. The ratio of the estimated first-pass count rate and the count rate in the same lung ROI after equilibration of the cells between the circulating and pulmonary pools (15-30 min) represents the PGP/TBGP. The technique was validated in eight subjects by using 99mTc-labeled macroaggregated human serum albumin. With corrections for background and injected doses, the ratios of first-pass granulocyte-to-macroaggregated human serum albumin count rates given by the three input ROIs were close to unity [superior vena cava 0.98 +/- 0.079 (SD), right ventricle 1.01 +/- 0.070, and pulmonary artery 0.97 +/- 0.073]. Significant increases in PGP/TBGP were demonstrated in systemic inflammation. Thus, in patients with inflammatory bowel disease, it was 0.22 +/- 0.07 (n = 7) compared with 0.08 +/- 0.01 (n = 5) in control subjects. It was also elevated in patients with systemic vasculitis (0.34 +/- 0.07; n = 5), in transplant recipients (0.33 +/- 0.08; n = 5), and in patients with osteomyelitis (0.15 +/- 0.06; n = 4). We conclude that this is a valid technique for quantifying the PGP that is expanded in several conditions associated with systemic inflammation.
Blood Flow Velocity↗
The effect of inhalation of platelet-activating factor on the pulmonary clearance of 99mTc-DTPA aerosol.
Platelet-activating factor (PAF) is a short-acting, lipid-soluble autocoid, inhalation of which causes an immediate pulmonary vascular sequestration of granulocytes and a peripheral neutropenia. We investigated the effect of PAF inhalation on the pulmonary clearance rate of inhaled 99mTc-DTPA in order to test the hypothesis that the pulmonary sequestration of granulocytes results in acute lung injury. In nine normal nonsmoking adults, the rate of clearance of DTPA, corrected for background activity, was 1.5 (SD 0.7) %/min over the first 10 min after inhalation. Inhalation of 4.8 micrograms PAF abruptly increased the clearance rate to a mean value of 2.3 (1.4) %/min (p < 0.05). No increase in clearance was observed in four nonsmoking subjects who inhaled vehicle only. The mean overall increase after PAF was 87% of the baseline clearance, significantly different (p < 0.05) from the corresponding change in the control group, which was -17%. After PAF, the clearance rate returned to baseline values within 10 min in all subjects. In all subjects who inhaled PAF, but in none who inhaled vehicle, there was an immediate neutropenia of 51 (SD 25) % of the baseline value (p < 0.01). This neutropenia persisted longer than the corresponding accelerated DTPA clearance and was still 74 (36) % of the baseline value at 10 min. Furthermore, there was no correlation between the increase in DTPA clearance induced by PAF inhalation and the decrease in peripheral blood granulocyte count. We conclude that PAF inhalation results in an increase in pulmonary DTPA clearance, probably not mediated by pulmonary vascular granulocyte sequestration.
Administration, Inhalation↗
The use of xenon-133 for measurement of blood flow through systemic arteriovenous malformations before and after therapeutic embolization.
Embolization is increasingly used to treat systemic arteriovenous (AV) shunts although its success, as judged by either angiographic or clinical means, is difficult to quantify. The aim of the study was to quantify blood flow through AV shunts with 133Xe, which, because of its relatively long transit time through peripheral tissues, behaves like microspheres. Following arterial injection, 133Xe entering an AV shunt rapidly arrives in the lung and can be quantified with a scintillation probe. In 17 patients with systemic AV shunts, the reduction in shunt flow following therapeutic embolization was quantified in the angiography theatre by comparing the initial count rates in the lung, recorded by probe, following injection of identical quantities of 133Xe into a supplying artery before and after embolization. By comparing the lung counts with those given by an intravenous injection of 133Xe, the fraction of flow at the catheter tip entering the shunt was also quantified. Tissue perfusion in the vascular territory distal to the shunt was measured at the same time by recording the clearance of non-shunted 133Xe with a second probe over the extremity. Control injections of 133Xe were given in the contralateral limb in order to assess 133Xe transit in the absence of shunting and to compare tissue perfusion between the two sides. Shunt flow ranged from 40% to 100% (of that at the tip of the catheter) (n = 14), while the reduction in shunt flow following embolization ranged from 15% to 96% (n = 19). Tissue perfusion distal to the shunt and in the contralateral limb was about 5 ml 100 ml-1 min-1. Contrast medium had no consistent effect on tissue perfusion in either limb, or on shunt flow. There was no difference in peripheral perfusion between the abnormal and control sides, nor any significant difference in perfusion in the distal tissue on the abnormal side before and after embolization. There was, however, a consistent increase in the fraction of the injected 133Xe delivered to the distal tissue after embolization (median increase 93%, p < 0.001). The technique is relatively simple and merits further development as a means of continuous quantification of systemic AV shunt flow in the angiography theatre at the time of embolization.
Adult↗
Pulmonary arteriovenous malformations: results of treatment with coil embolization in 53 patients.
OBJECTIVE: The purpose of this study was to determine the effects of percutaneous transcatheter coil embolization of pulmonary arteriovenous malformations on arterial oxygen saturation, pulmonary gas exchange, anatomic right-to-left shunt, and lung function and to assess the complications of the procedure. SUBJECTS AND METHODS: Fifty-three patients were included in the study: 42 (79%) had associated hereditary hemorrhagic telangiectasia. Nineteen (36%) had neurologic problems compatible with paradoxical embolization. During 102 separate embolization procedures, all malformations with feeding vessels > or = 3 mm in diameter were embolized with steel coils. Arterial oxygen saturation at rest and on exercise and the intrapulmonary right-to-left shunt fraction (99mTc-macroaggregate injection), forced expiratory volume in 1 sec, vital capacity, diffusing capacity for carbon monoxide, and transfer coefficient were measured before and after embolization. Complications of the procedure were recorded and investigated. RESULTS: Before treatment, all patients had hypoxemia in the supine posture (SaO2, 89 +/- 1% [standard error of the mean]), which fell a further 6% (absolute) on standing. Mean values for transfer coefficient and diffusing capacity for carbon monoxide were reduced, at 85 +/- 3% and 78 +/- 3% (predicted value), respectively. After embolization, the mean values for supine and erect SaO2 rose to 94 +/- 1% and 93 +/- 1%. Transfer coefficient increased by a mean of 5.4% of predicted value. The mean shunt fraction fell from 23 +/- 2% preembolization to 9 +/- 1% postembolization. In 102 procedures, there were 18 complications, 12 mild, two moderate, and four potentially serious (systemic coil embolization in two patients, cerebrovascular accident [transient], and myocardial puncture), but there were no lasting sequelae. CONCLUSION: Our results show that coil embolization is an effective and well-tolerated method for treatment of pulmonary arteriovenous malformations. Improvements in pulmonary gas exchange and lung function and a decrease in right-to-left shunting occurred after treatment. The procedure was well tolerated and had a low complication rate.
Adolescent↗
Granulocyte margination in bone marrow: comparison with margination in the spleen and liver.
The kinetics of radiolabelled granulocytes in the reticuloendothelial system were studied in order to evaluate granulocyte margination in bone marrow. A total of 34 patients took part in a two-part study. In the first part, bone marrow uptake of indium-111-labelled granulocytes was retrospectively analysed in early (3-h) and late (24-h) images in 26 patients, 13 with bronchiectasis and 13 with enclosed abdominal abscesses. The ratios between early and late counts from the bone marrow, spleen, liver and inflammatory lesion were used to quantify granulocyte margination in bone marrow, postulating that if the lesion to bone marrow ratio at 24 h exceeds the value at 3 h, then the "excess" bone marrow counts on the early images would represent margination. In the second part, this suggestion was prospectively tested using Rutland-Patlak graphical and deconvolution analysis of dynamic data, acquired in 8 patients undergoing routine scanning with technetium-99m HMPAO-labelled granulocytes. In the first part of the study, it appeared that the bone marrow is a regional site of granulocyte margination, like the spleen, with at least one-half of the 3-h marrow signal arising from marginated granulocytes, compared with about two-thirds from the spleen. In the second part, it was found that the gradient of the Patlak plot, based on spleen and marrow, continuously decreased, consistent with bi-directional movement of cells between these organs and the blood. Granulocyte pooling in the marrow was confirmed with deconvolution analysis, which generated biphasic retention functions for marrow and spleen. These curves were also consistent with two-way granulocyte exchange, and gave mean cell transit times in both organs of about 12 min and probabilities of extraction on each pass of 5-10%. We conclude that granulocytes marginate in bone marrow to an extent similar to that in the spleen.
Abdominal Abscess↗
Direct technetium-99m labeling of three anticancer monoclonal antibodies: stability, pharmacokinetics and imaging.
UNLABELLED: Monoclonal antibodies (MAbs) directly labeled with 99mTc have been used in a number of clinical immunoscintigraphic investigations. Three anti-cancer MAbs were radiolabeled with 99mTc using a reduction-mediated technique. The stability, biodistribution and in vivo pharmacokinetics were assessed and compared with the same antibodies labeled with 125I. METHODS: Immunoreactivity data were obtained by ELISA and RIA. Homogeneity and stability of radiolabeled antibodies (in vitro and in vivo) were measured by size-exclusion, fast protein liquid chromatography and SDS-PAGE. Pre-clinical, in vivo investigations utilized the nude mouse/HEp2 xenograft model, and clinical imaging and pharmacokinetic data were obtained from patients with confirmed or suspected lesions. RESULTS: Both 99mTc- and 125I-labeled antibodies were shown to be homogeneous and stable, although 99mTc-labeled antibody fragments were detected by SDS-PAGE. Pharmacokinetic studies in patients revealed a significant difference in the clearance rates between 99mTc- and 125I-labeled antibodies, with those labeled with 99mTc having a shorter biological half-life, indicating that the 99mTc-labeled antibodies may be less stable than the iodinated ones. Nevertheless, specific tumor localization was successfully demonstrated in nude mice bearing a human tumor xenograft using 125I- and 99mTc-labeled H17E2 antibody. Furthermore, in the clinic, using 99mTc-labeled HMFG1 and 1A3, successful imaging was achieved in 12 out of 19 patients with lesions for which these antibodies were specific. CONCLUSION: Anticancer MAbs radiolabelled using this reduction-mediated technique are suitable agents for clinical, immunoscintigraphic investigations.
Animals↗
Air enema radiology compared with leukocyte scintigraphy for imaging inflammation in active ulcerative colitis.
OBJECTIVE: To compare air enema radiology with a leukocyte scintigraphy technique using technetium-99m-hexamethyl propylene amine oxime-labelled leukocytes for imaging colonic inflammation in ulcerative colitis. DESIGN: Prospective study in a University hospital. One radiologist and one nuclear physician independently graded the degree of inflammation in six colon segments per patient using radiographs and leukocyte scans. PATIENTS: Twenty consecutive patients with symptoms of active ulcerative colitis requiring corticosteroids, inflammation on rigid sigmoidoscopy and a positive leukocyte scan above the rectum. RESULTS: Using air enema radiology, inflammation above the rectum was observed in 17 of the 20 patients. Eleven patients had the same extent of disease with both imaging techniques (total n = 5; extensive n = 3; distal n = 3). Seven patients had more widespread colitis using leukocyte scintigraphy. In the remaining two patients with extensive inflammation at scintigraphy, air enema films showed total colitis. When the colon was subdivided into six different segments, prediction of the presence of inflammation in individual segments was 0.88 for air enema radiology compared with leukocyte scintigraphy and 0.60 for the prediction of absence of inflammation. All segments with an irregular mucosal contour or ulceration on air enema films had intense inflammation at scintigraphy. CONCLUSIONS: In patients with active ulcerative colitis, air enema radiology underestimates the extent of inflammation because this investigation shows secondary patho-anatomical changes, while leukocyte scintigraphy visualizes the acute cellular infiltrate. In patients with more severe inflammation, there is excellent agreement between the two methods.
Adolescent↗
Simultaneous measurement of extracellular fluid distribution and renal function with a single injection of 99mTc DTPA.
BACKGROUND: The initial rate of renal uptake of 99mTc DTPA is equal to the product of injected dose and the glomerular filtration rate (GFR):plasma volume (PV) ratio, whilst later the plasma clearance rate constant is equal to the GFR:extracellular fluid volume (ECF) ratio. Expressing GFR in terms of body fluid volumes has several attractions, and techniques for measuring it in this form may be useful. METHODS: GFR/PV was determined from a Patlak plot in 82 studies in 47 patients undergoing routine gamma-camera 99mTc DTPA renography and compared with GFR/ECV, determined from the terminal slope of the plasma clearance curve. RESULTS: GFR/PV (y) correlated significantly with GFR/ECV (x): y = 3.2.x + 5.3 ml/min/l (r = 0.82, n = 82, P < 0.001). The ratio, GFR/PV:GFR/ECV is ECV/PV, which (x) correlated significantly with a regional estimate (y) of ECV/PV (rECV/rPV) derived from a Patlak plot applied to a subrenal ROI: y = 0.47x + 1.14 (r = 0.61, n = 52, P < 0.001). The initial rate constant of disappearance of 99mTc DTPA from the blood, determined from a ROI over the left ventricle, reflects tracer clearance from plasma to interstitial fluid plus GFR/PV: Subtraction of GFR/PV yields a rate constant which reflects extrarenal 99mTc DTPA clearance, Z, as a fraction of PV. A regional estimate of 99mTc DTPA clearance from plasma to interstitial fluid, rZ, was derived from the Patlak plot applied to the subrenal ROI and expressed in relation to rPV. Z/PV (y) correlated significantly with rZ/rPV (x): y = 2.2x + 0.02 min-1 (r = 0.56, n = 52, P < 0.001). The distribution of ECF between plasma and interstitial fluid was related to extrarenal 99mTc DTPA clearance. Thus rZ/rPV correlated significantly with ECV/PV (r = 0.55, n = 52, P < 0.001) and Z/PV correlated significantly with rECV/rPV (r = 0.6, n = 52, P < 0.001). There was no correlation between renal function and extrarenal 99mTc DTPA clearance or distribution of ECF. CONCLUSIONS: GFR can be measured in terms of PV and ECF volume from a single injection of 99mTc DTPA. ECV/PV, rECV/rPV, and variables representing the clearance of 99mTc DTPA across the microvasculature can be measured at the same time.
Adolescent↗
Medical complications of pregnancy in hereditary haemorrhagic telangiectasia.
Hereditary haemorrhagic telangiectasia (HHT) displays significant variation in severity between affected individuals in the same family, ranging from relatively trivial epistaxis and telangiectasia to gastrointestinal, cerebral and pulmonary involvement. Evidence for successful therapy of HHT-related haemorrhage with oestrogens and progesterones, and recent case reports outlining pulmonary complications of pregnancy in HHT, prompted us to review the outcome of 161 pregnancies in 47 affected women. HHT-related maternal complications developed in eleven patients, ten in the subgroup of 23 pregnancies in which pulmonary arteriovenous malformations (PAVMs) were present at the outset, or documented in the two years following pregnancy. We present six cases of intrapulmonary shunt deterioration, two cases of fatal pulmonary haemorrhage and three cerebrovascular accidents related to pregnancy. A predisposition towards PAVMs in females was observed. Following the recent discovery of mutations in the endoglin gene in this disease, our data support a hypothesis of hormonal modification of the HHT phenotype. In addition, a significant excess of affected offspring are present in HHT families. We consider contributary aetiological factors, and discuss implications for patient management.
Abortion, Spontaneous↗
Noninvasive imaging of E-selectin expression by activated endothelium in urate crystal-induced arthritis.
OBJECTIVE: To assess the expression of the cytokine-inducible endothelial leukocyte adhesion molecule E-selectin during the evolution of urate crystal-induced arthritis, using a recently described radiolabeled monoclonal antibody (MAb) imaging technique. METHODS: Monosodium urate (MSU) crystals and saline alone were injected respectively into the right (inflamed) and left (control) knees of 3 young pigs. Four hours later, 111In-labeled 1.2B6 F(ab')2 (anti-E-selectin MAb) and 125I-labeled MOPC 21 F(ab')2 (control MAb) were injected intravenously. Uptake of 1.2B6 in inflamed and control joints was assessed by scintigraphy 7 and 24 hours after intraarticular injection of MSU crystals. Immunohistochemistry studies and radioactivity counting of tissues were performed postmortem to confirm the observations from scintigraphy. RESULTS: MAb 1.2B6 F(ab')2 scintigraphic images of the knees revealed a significantly increased uptake in the right (inflamed) knee at 7 and 24 hours postinjection, particularly over the joint space. These in vivo images were consistent with E-selectin expression in the inflamed tissue detected by immunohistochemistry and with radioactivity counts postmortem. The synovial localization ratio (inflamed:control synovium counts) was 25.4 +/- 9.7 (mean +/- SD) for the anti-E-selectin MAb compared with 2.5 +/- 0.9 for the control MAb (P < 0.05, by paired Student's t-test). CONCLUSION: E-selectin is expressed by synovial endothelium during the evolution of urate crystal-induced arthritis and can be detected noninvasively using a radiolabeled MAb. This E-selectin imaging technique has considerable potential for the noninvasive assessment of endothelial activation in arthritis and other inflammatory rheumatic diseases.
Animals↗
Quantification of pulmonary uptake of indium-111 labelled granulocytes in inflammatory bowel disease.
This study describes a method for quantifying the pulmonary trapping of indium-111 labelled polymorphonuclear (PMN) cells in patients with inflammatory bowel disease (IBD) in comparison to non-inflamed controls. Twenty patients with extensive IBD were studied by 111In-PMN scintigraphy. Gamma-camera images were obtained at 2.5-4 h (early) and 20-25 h (late) after the injection of autologous PMNs labelled in plasma with 111In-tropolonate. Local uptake in the chest, iliac bone marrow, spleen and liver was quantified as the counts per pixel per second per MBq of injected 111In for both early and late scans. Fourteen subjects without inflammatory disease were studied as controls. IBD patients showed significantly greater loss of splenic activity between early and late scans compared with controls (mean +/- SD: -35.7% +/- 16.6% versus -4.5% +/- 6.1%, P < 0.001). There was no significant difference between control and IBD groups with respect to liver and bone marrow uptake on both early and late scans. Chest uptake was significantly higher in patients with IBD on both early (6.4 +/- 1.6 cps/MBq/pix) and late (5.6 +/- 1.5 cps/MBq/pix) scans, compared with the controls (4.8 +/- 1.3 cps/MBq/pix, P < 0.005 and 3.4 +/- 1.0 cps/MBq/pix, P < 0.001 respectively). The chest uptake in the control group on the late scans demonstrated a significant linear correlation with iliac uptake (y = 0.23x + 0.41, r = 0.87, n = 14). Assuming in controls that there is no parenchymal uptake of 111In, this regression enables an estimate to be made, based on iliac counts, of the count rate from bone marrow in the chest wall.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Measurement of the ratio of glomerular filtration rate to plasma volume from the technetium-99m diethylene triamine pentaacetic acid renogram: comparison with glomerular filtration rate in relation to extracellular fluid volume.
Individual kidney glomerular filtration rate (IKGFR) can be measured from the renogram from the rate of uptake of technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA). A blood sample is required to derive IKGFR in millilitres per minute, which is then usually normalised to body surface area. We describe a technique which does not require a blood sample, is already normalised for plasma volume and uses the robust Patlak plot for measuring renal uptake. The rate of kidney uptake, dR(t)/dt, at time = 0, as a fraction of the injected dose, is equal to the fraction of the plasma volume (PV) filtered per minute, i.e. IKGFR/PV. The gradient dR(0)/dt cannot be accurately measured directly but is equal to [alpha .LV(0)], where alpha is the renal uptake constant (proportional to IKGFR) and LV is the count rate over a left ventricular ROI. LV(0) was obtained by extrapolation of LV(t), while alpha is the slope of the Patlak plot up to 3 min. GFR/PV (i.e. right plus left kidneys) in patients with normal renal function was about 0.04 min-1, as would be expected from normal values of GFR (120 ml/min) and plasma volume (3 l). GFR/PV correlated significantly with the ratio of GFR to extracellular fluid volume (ECV), measured from the terminal exponential of the plasma clearance curve (GFR/PV = 3.2.GFR/ECV + 5.3 ml/min/l [r = 0.82, n = 82]). GFR/PV (r = 0.74) and GFR/ECV (r = 0.82) both correlated inversely and non-linearly with plasma creatinine in 43 studies where the measurement was made within 1 week of the 99mTe-DTPA study.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
The utility of [99mTc]HMPAO-leukocytes for imaging infection.
Technetium-99m hexamethylpropylene amine oxime (HMPAO)-labeled leukocytes are well established for the investigation of inflammatory disease. Their kinetics and normal distribution are similar to those of indium-111-labeled leukocytes except for nonspecific activity in urine, kidneys, gall bladder, and bowel, which results from the elution of secondary 99mTc-labeled HMPAO complexes. The principal clinical indications for [99mTc]HMPAO-leukocytes include inflammatory bowel disease (IBD), osteomyelitis, soft tissue sepsis, and, to a lesser extent, occult fever. The superior resolution and count density of 99mTc places [99mTc]HMPAO-leukocytes at an advantage over 111In-leukocytes in IBD, especially for the identification of small bowel involvement in patients with Crohn's disease. However, quantification of disease activity is more difficult than with 111In. Technetium-99m HMPAO-leukocytes are indicated for most forms of acute soft tissue and abdominal sepsis, although when compared with 111In, it may be more difficult to demonstrate communication between an abdominal abscess and bowel lumen. Chronic osteomyelitis, including infected joint prostheses, are better approached with 111In-labeled leukocytes. Occult fever and fever of unknown origin (FUO) are more controversial. There is still a place for gallium-67 in FUO, of which there is a wide spectrum of causes. Occult fever implies a pyogenic cause for an undiagnosed fever and should probably be imaged with 111In-leukocytes. With the advances being made in other imaging modalities and in interventional radiology, there is a clear need for radionuclide agents that can be used for whole-body screening in patients with undiagnosed fever. Such agents may include fluorine-18-fluorodeoxy-glucose and radiolabeled monoclonal antibodies to endothelial adhesion molecules activated at the foci of inflammation.
Bone and Bones↗
Role of the spleen in leucocytosis after exercise.
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Exercise↗
Measurement of the extravascular concentration of renal agents following intravenous bolus injection.
The extravascular concentration (Ce) of some renal agents, in relation to the simultaneous plasma concentration (Ci), was calculated as a function of time after intravenous injection. Four agents were studied: 51Cr-ethylenediamine tetraacetate (EDTA) (n = 11), 125I-hippuran (n = 11), 99Tcm-dimercaptosuccinic acid (DMSA) (n = 11) and 99Tcm-mercaptoacetyl triglycine MAG3 (n = 20). Plasma clearance curves were constructed from data acquired from multiple blood sampling and fitted with two exponentials. The extravascular content of tracer at any time is equal to the injected dose remaining after subtraction of the intravascular tracer content and the total amount of tracer cleared from plasma. Mean Ce/Ci at equilibrium (defined as the time, > 120 min, when Ce/Ci reaches its maximum value) was 1.087 (S.D. 0.019) for EDTA, 1.73 (0.48) for hippuran, 0.37 (0.2) for DMSA and 0.64 (0.3) for MAG3. Corresponding clearance (F) values were 68 (13), 415 (149), 15.6 (9.5) and 214 (52) ml min-1 1.73 m-2. Ce/Ci correlated with F and was also related to protein binding in plasma. Extrapolation of the regressions of Ce/Ci on F to F = 0 at several time points after injection gives a curve of Ce/Ci (at F = 0) against time which represents the rate of equilibration of the tracer throughout its distribution volume that would be seen with zero clearance, and therefore allows measurement of the in vivo protein binding of the tracer in plasma. Protein binding was zero for EDTA, 30% for hippuran, 86% for DMSA and 88% for MAG3.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Graphical analysis of dynamic data: the Patlak-Rutland plot.
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Glomerular Filtration Rate↗