Extravascular chest wall technetium 99m diethylene triamine penta-acetic acid: implications for the measurement of renal function during renography

Measurement of individual kidney glomerular filtration rate (IKGFR) from the gamma-camera technetium 99m diethylene triamine penta-acetic acid (^99mTc-DTPA) renogram requires a continuous measurement of arterial activity. This is usually based on a region of interest (ROI) placed over the cardiac blood pool on the posterior view, with the assumption of negligible contamination from activity in the extravascular space of the chest wall. By injecting a small dose of technetium 99m human serum albumin (HSA) before the^99mTc-DTPA in 12 patients undergoing routine renography, the contribution of extravascular activity to the total signal recorded over the cardiac blood pool was calculated to be 11.0% (SE 2.1%) 1.5 min after DTPA injection, rising to 35.1% (SE 2.5%) at 15 min. Subtraction of the time-activity curve recorded from a ROI of the same size over the right lung generated a pure blood signal as shown by almost identical HSA/DTPA signal ratios recorded in blood samples taken 5 min after HSA and 15 min after DTPA and from the gamma-camera at the corresponding times. The effect of using a cardiac blood pool time-activity curve uncorrected for extravascular activity was to overestimate IKGFR by an average factor of 1.17 (SE 0.03). Offprint requests to: A.M. Peters     

Background in 99Tcm DTPA renography evaluated by the impact of its components on individual kidney glomerular filtration rate

Following injection for renography, 99Tcm-labelled diethylenetriamine-pentacetic acid (DTPA) rapidly enters the extravascular space. Background therefore comprises two components, a falling intravascular signal and an extravascular signal which initially rises. We estimated the relative magnitudes of these two components in terms of their impact on the calculation of differential renal function and individual kidney glomerular filtration rate (IKGFR) from the second phase of the 99Tcm-labelled DTPA renogram in 56 paediatric kidneys. We expressed each of the two background signals as a GFR equivalent. The GFR equivalent of the intravascular signal recorded from a peri-renal background region of interest (ROI), scaled by a factor equal to the ratio of the pixel numbers in the renal and background ROIs, was -39 (S.D. 14) ml min-1. The GFR equivalent of the extravascular signal was smaller than this and opposite to it at 23 (S.D. 10) ml min-1, giving a median ratio for the two equivalents of -1.68. Because of the opposing effects of the two background components on the second phase of the renogram, techniques recently described for the quantification of IKGFR from the renogram, and which eliminate the intravascular component, offer no theoretical advantage over a method of analysis which uses 'direct' subtraction of the total background signal. In practice, however, these new techniques are superior in their handling of 'noisy' data, consistently giving a lower coefficient of variation in their estimation of IKGFR.     

Technetium 99m mercaptoacetyltriglycine gamma camera clearance calculations: methodological problems.

Major sources of errors in the gamma-camera methods for the calculation of renal clearance are the accuracy of background correction for obtaining the true renal time-activity curve and the validity of the externally recorded pre-cordial activity as an estimate of the plasmatic time-activity curve. With technetium 99m mercaptoacetyltriglycine (99mTc-MAG3), because of its high protein plasma binding, one could expect minimal extravascular diffusion and hence a more accurate externally detected plasmatic curve. The high extraction rate should reduce the influence of the background, but, on the other hand, the effect of hepatobiliary excretion on the calculation of renal clearance might be significant. Our results suggest that the hepatobiliary excretion of 99mTc-MAG3 does not influence the gamma-camera renal clearance determination, even in patients with low renal function. However, the pre-cordial curve does not reflect accurately the plasmatic disappearance curve; its calibration with a single plasma sample taken at the 20th min is responsible for significant errors, probably because of an unfavourable ratio between the intravascular and extravascular activities at the 20th min.     

Technetium 99m mercaptoacetyltriglycine gamma camera clearance calculations: methodological problems

Major sources of errors in the gamma-camera methods for the calculation of renal clearance are the accuracy of background correction for obtaining the true renal time-activity curve and the validity of the externally recorded pre-cordial activity as an estimate of the plasmatic time-activity curve. With technetium 99m mercaptoacetyltriglycine (^99mTc-MAG3), because of its high protein plasma binding, one could expect minimal extravascular diffusion and hence a more accurate externally detected plasmatic curve. The high extraction rate should reduce the influence of the background, but, on the other hand, the effect of hepatobiliary excretion on the calculation of renal clearance might be significant. Our results suggest that the hepatobiliary excretion of^99mTc-MAG3 does not influence the gamma-camera renal clearance determination, even in patients with low renal function. However, the pre-cordial curve does not reflect accurately the plasmatic disappearance curve; its calibration with a single plasma sample taken at the 20th min is responsible for significant errors, probably because of an unfavourable ratio between the intravascular and extravascular activities at the 20th min. Offprint requests to: M. TondeurParts of this work have been presented at the 17th Annual Meeting of the British Nuclear Medicine Society, London, in April 1989.     

Visualizing cardiac blood pool: Comparison of three labeling methods

The quality of three different labeling methods of visualizing the cardiac blood pool was investigated in 72 patients:^99mtechnetium labeling of red blood cells in vivo or in vitro and human serum albumin. By the simplified technique of in vitro labeling of RBC from the view point of (1) labeling efficiency, (2) activity in the blood, (3) count rates in a standard ROI over the left ventricle and the paracardiac background, (4) ratio of these count rates, and (5) evaluation of image quality, the best results were obtained. HSA and in vivo labeled RBC led to satisfactory results for visual assessment of ventricular performance in most cases. In spite of the slightly higher technical investment involved in the in vitro labeling method this technique appears to be preferable for gated cardiac blood pool studies in view of the excellent labeling quality.     

99mTc-DTPA gamma-camera renography: normal values and rapid determination of single-kidney glomerular filtration rate

A method for 99mTc-diethylenetriaminepentaacetate (DTPA) gamma-camera renography is presented. From each renogram, an uptake index (UI) proportional to the single-kidney glomerular filtration rate (SKGFR) is defined. If the proportionality factor between UI and SKGFR is the same in all patients, UI can be used as an accurate measure of SKGFR. In order to test this, 99mTc-DTPA renography was performed in 101 patients with glomerular filtration rates (GFR) varying between 4 and 172 ml/min. The sum of the right- and left-kidney UIs correlated well with the total GFR calculated from the simultaneously measured plasma clearance of 99mTc-DTPA after a single injection. The correlation coefficient was 0.97. The method was tested in a prospective study of 57 patients. The total GFR estimated from the renograms was not significantly different from the GFR calculated from the plasma clearance of 99mTc-DTPA. The coefficient of variation--a combination of inaccuracy and imprecision in the estimates as well as in the reference values-was 11.8% at a GFR of 100 ml/min. It is concluded that, in adults, the SKGFR can be calculated as part of the clinical routine from 99mTc-DTPA gamma-camera renography without determining the injected dose or collecting urine or blood samples. Normal values for some parameters of the renogram obtained in 25 normal subjects are given.     

Measurement of the distribution volume of gadopentetate dimeglumine at echo-planar MR imaging to quantify myocardial infarction: comparison with 99mTc-DTPA autoradiography in rats.

PURPOSE: To measure the fractional distribution volume of gadopentetate dimeglumine in normal and reperfused infarcted myocardium at magnetic resonance (MR) imaging by using the fractional distribution volume of technetium 99m-diethylenetriaminepentaacetic acid (DTPA) as an independent reference. MATERIALS AND METHODS: Rats were subjected to 1 hour of coronary artery occlusion and 1 hour of reperfusion before inversion-recovery echo-planar imaging or autoradiography. Regional change in relaxation rate (delta R1) ratios for myocardium over blood were compared with radioactivity ratios for myocardium over blood after the injection of 99mTc-DTPA. RESULTS: Both delta R1 and radioactivity ratios demonstrated equilibrium distribution and hence represent partition coefficients (lambda). The fractional distribution volumes were greater in infarcted myocardium (0.90 +/- 0.05 for gadopentetate dimeglumine and 0.89 +/- 0.04 for 99mTc-DTPA) than in normal myocardium (0.23 +/- 0.02 for gadopentetate dimeglumine and 0.16 +/- 0.01 for 99mTc-DTPA). Area at risk at autoradiography was not significantly different from that at histomorphometry. The infarction size defined by using triphenyltetrazolium chloride was 13% +/- 4 smaller than that defined by using autoradiography. CONCLUSION: The fractional distribution volumes of gadopentetate dimeglumine and 99mTc-DTPA are similar and indicate extracellular distribution in normal myocardium and intracellular as well as extracellular distribution in reperfused infarction. Because the failure of cells to exclude these agents is indicative of necrosis, contrast medium-enhanced MR imaging may be useful to quantify myocardial infarction.     

Comparison of radionuclide estimation of glomerular filtration rate using technetium 99m diethylenetriaminepentaacetic acid and chromium 51 ethylenediaminetetraacetic acid

Simultaneous measurements of the clearance rates of technetium 99m diethylenetriaminepentaacetic acid (99mTc-DTPA) and chronium 51 ethylenediaminetetraacetic acid (51Cr-EDTA) were performed in 30 patients with a range of renal function (glomerular filtration rates between 9 and 120 ml/min). Using multiple blood samples, the two clearance values correlated well (r = 0.991, standard error 3.9 ml/min), but DTPA clearance was systematically higher by 7.6%. For each radiopharmaceutical, an equation was derived to correct clearance values obtained using only plasma samples taken at 2 and 4 h for the systematic error inherent in this technique compared with analysis of the complete plasma concentration-time curve. The root mean square error remaining after application of these equations was 1.9 ml/min for both the EDTA and DTPA data. The corresponding errors obtained using the equation derived by Brochner-Mortensen for EDTA plasma clearance were 2.2 ml/min and 1.9 ml/min, respectively, these values were not significantly different from those obtained using the equations derived in this study.     

Comparisons of the time-activity curves of the cardiac blood pool and liver uptake by99mTc-GSA dynamic SPECT and measured99mTc-GSA blood concentrations

OBJECTIVES: The aim of this study was to determine the time-activity curve in the cardiac and hepatic region by 99mTc-GSA dynamic SPECT which is clinically used in liver scintigraphy and evaluate the temporal changes in the consistency and errors at the absolute scale using the regression equation of changes in the blood concentration of 99mTc-GSA. METHODS: In 11 patients who underwent 99mTc-GSA dynamic SPECT over the 30 min period after IV injection, the percentages of activity in the collected blood and in the blood pool estimated by dynamic SPECT were determined as the plasma clearance by blood collection and as the blood clearance by cardiac pooling. Extrahepatic uptake, expressesd as 100--(% uptake in the liver by dynamic SPECT (%)) was calculated as the blood clearance by the liver. The regression equation (Y = Y0 + Ae(-alphat)) was determined from the changes in the counts, expressed as a percent. Percent errors and the differences in the Y-intercept (Y0), coefficient (A) and slope (alpha) on the regression curve were compared. RESULTS: Blood pool clearance gradually exceeded the measured plasma clearance. The clearance by the liver started from a very low initial value and gradually became equal to that of plasma clearance over the first 15 minutes and exceeded it over the second 15 minutes. The Y-intercept was significantly higher in the blood pool clearance than that in the measured plasma clearance (p < 0.001), and the coefficient was significantly lower in the former than the latter (p < 0.001). The coefficient and slope were significantly lower in the hepatic clearance than the plasma clearance (p < 0.001, p < 0.005). Conclusion: The time-activity curve of the blood pool showed a tendency towards overestimation in the second half of the examination, probably due to scatter effect from the liver. The time-activity curve of liver uptake showed a tendency towards overestimation in the first half of the examination, probably due to the high concentration in the hepatic blood pool, and underestimation in the second half.     

The APE nebuliser--a new delivery system for the alveolar targeting of particulate technetium 99m diethylene triamine penta-acetic acid

We report the validation of a new delivery system--aerosol production equipment (known by the acronym APE), which generates a particulate aerosol of technetium 99m diethylene triamine penta-acetic acid (DTPA) with a mass-median aerodynamic diameter of 0.35 microns and a geometric standard deviation of 1.8 Twenty subjects were studied; in group 1 were 12 healthy men with normal spirometry; in group 2 were 8 men with AIDS who had mildly abnormal lung function following an episode of pneumocystis pneumonia-spirometry FEV1 3.08 (0.73) L, FVC 4.83 (0.82) L [mean (SD)]. The APE nebulizer was used to form a particulate aerosol with 200 MBq of 99mTc DTPA, which was collected in a 35 1 reservoir of air, which was subsequently inhaled. The mean (SD) inhalation time was 4.7 (0.44) min. The output of the nebulizer (% of activity inhaled) was 82%. Using planar imaging, the penetration index (right lung) in group 1 was 0.93 (0.18), mean (SD), and in group 2 it was 0.91 (0.12). There was virtually no tracheal deposition and extrapulmonary deposition (oropharynx and stomach) was less than 5% of the aerosol delivered. Single-photon emission tomography (SPET) studies carried out in five patients from group 1 confirmed homogeneous intrapulmonary deposition of 99mTc-DTPA. In view of the excellent intrapulmonary deposition of 99mTc-DTPA produced by the APE nebulizer, it may provide an alternative to conventional ventilation studies using radioactive gases.     

Two routes for 99mTc-DMSA uptake into the renal cortical tubular cell

Critical factors determining the renal handling of 99mTc-dimercaptosuccinic acid (DMSA) are protein binding in plasma and the renal 99mTc-DMSA extraction efficiency. Comparison of the count rate over soft tissue with that over the cardiac blood pool about 1 h after injection demonstrated that 99mTc-DMSA is not exclusively an intravascular label. 99mTc-DMSA was 76% protein bound in plasma as demonstrated by HPLC and gel filtration. Assuming that the 24% that is not protein bound is filtered at the glomerulus, the renal extraction efficiency of 99mTc-DMSA by glomerular filtration is about 5%. Since the total renal extraction efficiency was also found to be about 5%, the majority of the activity that becomes fixed in the renal cortex arrives there as a result of filtration followed by tubular reabsorption rather than by direct extraction from peritubular blood. However, discordant changes in DMSA and DTPA uptake induced by captopril in renovascular hypertension (RVH) suggested that a minority of uptake was by direct peritubular extraction. This kinetic model was supported by indirect measurement of protein binding and extraction efficiency based on the kinetics of 99mTc-DMSA disappearance from plasma and kinetics of uptake in the kidneys. Furthermore, differential functional studies based on 99mTc-DMSA and 99mTc-DTPA before and after captopril in patients with RVH due to unilateral renal artery stenosis confirmed filtration followed by tubular reabsorption as the predominant route for DMSA uptake by the kidney.     

Technetium Tc 99m plasmin in the diagnosis of inflammatory disease

The localization characteristics of technetium Tc 99m plasmin were studied in experimental animals to investigate the use of 99mTc-plasmin for imaging inflammatory processes. At various times after abscess induction using turpentine in rats, the in vivo distribution properties of 99mTc-plasmin, gallium citrate Ga 67, 125I-fibrinogen, and 99mTc-human serum albumin (HSA) were studied by gamma-camera imaging. The in vivo binding of each radiopharmaceutical was also tested in rat and human plasma clots. Region-of-interest analyses of gamma-camera images showed relatively poor 99mTc-plasmin localization at sites of abscess formation. The ratio of abscess-to-control activity of this radiopharmaceutical did not exceed that of 67Ga, 125I-fibrinogen, or 99mTc-HSA. In vitro assays of each of the radiopharmaceuticals in plasma clots showed 99mTc-plasmin and 125I-fibrinogen to have the best localization characteristics.     

Technetium-99m DTPA renal flow studies in Goldblatt hypertension

Computer-assisted dynamic renal studies were performed on a group of 14 mongrel dogs before and after the induction of unilateral renal artery stenosis. Ninety-second technetium-99m diethylenetriaminepentaacetic acid ( [99mTc]DTPA), 15-min [99mTc]DTPA, and 30-min iodine-131 orthoiodohippurate ( [131I]hippuran) time-activity curves were analyzed and correlated with reduction of renal blood flow as measured by electromagnetic flow probe and PAH clearance techniques. Parameters of the 90-sec [99mTc]DTPA curves found to be significantly different for the same kidney before and after stenosis were: upslope, curve width at 75% maximum, maximum activity value, and differential (stenotic/contralateral) maximum activity ratio. For blood flow reductions greater than 33%, the [99mTc]DTPA studies were judged diagnostic of unilateral renal artery stenosis in all cases, whereas the [131I]hippuran time-activity curves were indicative of stenosis in only six of ten studies. Thus, in this model we find the computer-assisted 90-sec [99mTc]DTPA renal flow study to be superior to conventional [131I]hippuran renography in the diagnosis of moderate-to-severe unilateral renal artery stenosis.     

Appropriate selection of background for 99Tcm-DTPA renography

Since 99Tcm-DTPA is diffusible and not significantly protein bound in plasma, it rapidly enters the extravascular space following injection. Therefore, during the first few minutes of the DTPA renogram, the period on which the measurements of individual kidney glomerular filtration rate and differential function are based, background activity comprises a rising extravascular signal and a falling intravascular signal. The aim of this study was to measure the ratio of these two signals in background present within the renal region of interest (ROI) and compare it with the ratio in a background ROI. An appropriate background ROI is one in which the ratio is equal to that in background in the renal ROI. To pursue this aim, we quantified the rates of change of the intravascular and extravascular activities in background and, by comparing them with the rate of increase of filtered activity, expressed them as GFR equivalents (the intravascular being negative). It is impossible, from a single renogram, to separate the rising extravascular signal from the signal due to filtered activity, and therefore impossible to quantify the extravascular GFR equivalent present in background within the renal ROI. We therefore studied six patients undergoing bone marrow transplantation before and after cyclosporin treatment. By comparing the dynamic renographic data between the two sequential studies, the substantial fall in GFR (from 107 +/- 12 S.D. to 49 +/- 7 ml min-1) permitted separate quantification of the extravascular GFR equivalent in the renal ROI in both studies. Three of the patients were studied on a third occasion after cyclosporin. In two, GFR remained low and these studies were paired with corresponding baseline studies, while in the other it increased and this was compared with the nephrotoxic study, giving a total of nine paired studies between which GFR changed. The ratio of intravascular to extravascular GFR equivalents in a background ROI placed above the kidney was considerably greater, and in a background ROI below the kidney considerably less, than that in the renal ROI. A background ROI which was the difference between the renal ROI and a perirenal ROI, 2 pixels outside the renal ROI along the horizontal and 1 pixel outside along the vertical, gave a ratio almost identical to that of the background within the renal ROI (renal ROI ratio:background ROI ratio = 1.09 +/- 0.17 S.D., n = 18).(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of region assignment on relative renal blood flow estimates using radionuclides

To determine the value of the initial phase of the Tc-99m DTPA renogram in the direct estimation of relative renal blood flow in dogs, the ratios of the slopes of renal time-activity curves were compared with the ratios of measured blood flow. Radionuclide results were dependent on region-of-interest (ROI) and background ROI assignment, and correlated well with measured relative flow only with a maximum renal outline region. Curve slope ratios correlated well with measured flow ratios with and without background correction, while 1- to 2-minute uptake ratios correlated well only when corrected for background.     

An evaluation of six kits of technetium 99m human serum albumin injection for cardiac blood pool imaging.

We have investigated the suitability of five different commercially available kits which provide human serum albumin (HSA) labelled with technetium 99m (99mTc) for cardiac blood pool imaging. Four of these products were one-step processes using stannous chloride as the reducing agent; the fifth was based on an electrolytic reduction. In addition, we also assessed our own modification of the electrolytic method. We measured the radiochemical purity by precipitation with trichloroacetic acid and by gel filtration on a Biogel P4 column. In addition, we measured the clearance of radioactivity from the blood at frequent time intervals after intravenous injection. Each product was assessed in separate groups of six patients. The labelling efficiency of the one-step kits varied between 73 and 93% compared with 94 and 98% for the electrolytically labelled albumin. The blood clearance for all one-step kits was significantly faster than that obtained for the radiopharmaceuticals prepared by the electrolytic method. We conclude that HSA labelled with 99mTc by the electrolytic method is to be preferred.     

Dynamic three-dimensional MR renography for the measurement of single kidney function: initial experience

A three-dimensional magnetic resonance (MR) renographic method to measure single kidney glomerular filtration rate (GFR) and split renal function was developed that is based on renal signal intensity measurements during 2-3 minutes after intravenous injection of a low dose (2 mL or 0.01 mmol/kg) of gadopentetate dimeglumine. In nine subjects, single kidney MR GFR indices correlated well with technetium 99m (99mTc) diethylenetriaminepentaacetic acid (DTPA) clearance (r = 0.7-0.8) for GFR values of 7-48 mL/min. MR right kidney split renal function values (range, 32%-59%) also correlated well with 99mTc-DTPA radionuclide measurements (r = 0.76); differences between the two methods averaged 0.8% +/- 8. MR renography was performed along with contrast material-enhanced MR imaging of the kidneys and renal arteries and added 8 minutes or less to the total examination time.     

An evaluation of six kits of technetium 99m human serum albumin injection for cardiac blood pool imaging

We have investigated the suitability of five different commercially available kits which provide human serum albumin (HSA) labelled with technetium 99m (^99mTc) for cardiac blood pool imaging. Four of these products were one-step processes using stannous chloride as the reducing agent; the fifth was based on an electrolytic reduction. In addition, we also assessed our own modification of the electrolytic method.We measured the radiochemical purity by precipitation with trichloroacetic acid and by gel filtration on a Biogel P4 column. In addition, we measured the clearance of radioactivity from the blood at frequent time intervals after intravenous injection.Each product was assessed in separate groups of six patients. The labelling efficiency of the one-step kits varied between 73 and 93% compared with 94 and 98% for the electrolytically labelled albumin. The blood clearance for all one-step kits was significantly faster than that obtained for the radiopharmaceuticals prepared by the electrolytic method. We conclude that HSA labelled with^99mTc by the electrolytic method is to be preferred.     

First-pass radionuclide determination of cardiac output: an improved gamma camera method

A technique for noninvasive determination of cardiac output by aid of first-pass radionuclide cardiography is described. After intravenous injection of 10-15 mCi technetium-99m-(99mTc) labeled red blood cells the method requires acquisition of a first passage time-activity curve recorded with a gamma camera over the left ventricle, the background corrected left ventricular count rate recorded after complete mixing of the tracer in the circulation, and determination of the distribution volume of the tracer. The method was applied in 14 patients with heart disease of various origins and evaluated against the conventional tracer dilution technique with arterial sampling of blood activity. Cardiac output determinations by external counting ranged from 2.30 to 8.56 l/min, mean +/- s.d. 4.50 +/- 1.66 l/min and by arterial blood sampling from 1.88 to 8.96 l/min, mean +/- s.d. 4.52 +/- 1.71 l/min. An excellent correlation was demonstrated between the two techniques, r = 0.978 (p less than 0.001). When no background subtraction was applied to the left ventricular counts at equilibrium, radionuclide cardiac output values were approximately 40% higher than those obtained by arterial sampling. The new first-pass radionuclide cardiographic technique may prove a useful tool in the noninvasive evaluation of cardiac function, especially in patients with arrhythmias and/or valvular incompetence.     

Forearm blood flow measurements using technetium-99m human serum albumin following brachial arteriotomy

A simple, low cost method for measuring forearm blood flow during reactive hyperemia has been developed. Subjects are seated with hands and forearms over a large field-of-view gamma camera. Blood pressure cuffs inflated above the elbows isolate the blood in the forearms and hands and induce a hyperemic response. The remaining blood pool is labeled with technetium. The rate of increase of activity following release of the cuffs is measured from the gradient of time-activity curves and is calibrated for flow by counting a venous blood sample. The technique has been applied to a group of normal controls and to symptomatic and asymptomatic patients following right brachial arteriotomy. Forearm blood flow in normal subjects was 32.9 +/- 6.4 ml/100 ml/min and for subjects with occlusion of the brachial artery was 6.4 +/- 2.1 ml/100 ml/min. The method is simple, widely available, and reproducible. The good signal to noise ratio allows it to be used in cases of very low flow either as an aid to diagnosis or to measure treatment response.