Comparison of 99mTc-mercaptoacetyltriglycine and [131I]-o-iodohippurate elimination in perfused rat kidney.

Renal elimination of two renal radiodiagnostic agents, (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3) and [(131)I]-o-iodohippurate (OIH) has been studied using the method of the perfused rat kidney. The experiments showed significant differences between renal handling of (99m)Tc-MAG3 and OIH in the perfused rat kidney. While the renal clearance for (99m)Tc-MAG3 was relatively stable, the renal clearance values of OIH rapidly decreased after the OIH administration in a bolus dose. The infusion administration of OIH resulted in stable clearance values during the perfusion. The OIH/(99m)Tc-MAG3 renal clearance ratio was 2.47. Both compounds were bound to proteins in the perfusate to a considerable extent. An analysis of renal handling showed that contribution of tubular secretion to the total excretion was 95% for OIH, and 97% for (99m)Tc-MAG3.

Validation of the preparation of individual doses of (131)I-sodium o-iodohippurate ((131)I-hippuran).

The preparation of low activity doses of (131)I-hippuran has a drawback due to its high radioactivity concentration. In this study we diluted the radiopharmaceutical with saline or phosphate buffered saline (PBS) in order to decrease the radioactivity concentration, facilitate the preparation of individual doses and validate these procedures. We prepared doses of approx. 1.85 MBq of (131)I-hippuran from 10 different batches the day before the calibration date: undiluted, and diluted 1:9 with saline or PBS. The radiochemical purity (RCP) was evaluated the day after the expiration date. The percentage of (131)I-hippuran retained on syringes was assessed in vitro, after emptying the syringe and washing it twice with water (n=3 x 27); and in vivo, after the endovenous administration of the dose and washing the syringe twice with the patient's blood (n=3 x 75). Sterility was assessed using fluid thyoglicolate medium (n=3 x 15). All RCP values were greater than those required by the European Pharmacopoeia (>96%) except one of the undiluted (131)I-hippuran (95.8%) doses. No statistical difference was observed among them. The mean undiluted (131)I-hippuran retained in vitro was 5.4% (SD=6.5%), statistically greater (P<0.01) than both saline diluted (mean=1.5%, SD=1.1%) and PBS diluted (mean=2.0%, SD=2.4%). The mean undiluted (131)I-hippuran retained in vivo was 6.4% (SD=5.4%), statistically greater (P<10-5) than both saline diluted (mean=3.1%, SD=2.3%) and PBS diluted (mean=3.1%, SD=3.1%). We concluded that: (1) the dilution of (131)I-hippuran with saline or PBS makes both the preparation of individual doses and its administration to the patient easier without decreasing its radiopharmaceutical quality; and (2) using saline or PBS diluted (131)I-hippuran the percentage of radiopharmaceutical retained on the syringes, after use, is minimized.

Simplified methods for estimation of 99mTc-pentetate and 131I-orthoiodohippurate plasma clearance in dogs and cats.

The purpose of this study was to evaluate simplified methods for estimation of Technetium Tc 99m (99mTc)-pentetate and orthoiodohippurate I 131 (131I-OIH) plasma clearance in dogs and cats with 1 and 2 blood samples. Plasma clearances were calculated after a bolus injection of 1.85-11.1 MBq of 99mTc-pentetate and 131I-OIH with a 2-compartment model based on a 12-point curve as a reference method in 21 dogs and 18 cats. Three 2-sample and 3 single-sample methods were investigated. The method yielding the smallest standard deviation of the difference between the reference method and the simplified method was selected as the optimal one. Linear regression analysis was performed between the reference method and the simplified method and coefficient of determination (R2) was calculated. For 99mTc-pentetate plasma clearance, the optimal 2-sample method was the one with a mono-compartment model with samples taken at specific times. For 131I-OIH plasma clearance, the estimation was improved slightly by raising the clearance calculated with a mono-compartment model to the power of an empirically determined parameter. The optimal single-sample method was the one with a linear quadratic regression between the volume of distribution of the tracer at a specific time and the clearance calculated with 12 samples. Two-sample methods performed significantly better than did single-sample methods. The conclusion is made that 99mTc-pentetate and 131I-OIH plasma clearances can be estimated in dogs and cats with 1 or 2 blood samples with a reasonable margin of error compared to plasma clearances calculated with a 2-compartment model and 12 blood samples.

Can continuous intraperitoneal infusion of 125I-iothalamate and 131I-hippuran be used for measurement of GFR in conscious rats?

We previously described a method to measure GFR in conscious spontaneously voiding rats. This method circumvents the need for anesthesia and for bladder instrumentation. It's main principle is the correction of renal 125I-iothalamate clearance for incomplete urine collection by the ratio of plasma and renal clearance of co-infused 131I-Hippuran. A disadvantage of this technique is the requirement of an intra-arterial catheter for infusion of the renal function tracers. We therefore tested whether intraperitoneal infusion of 125I-iothalamate and 131I-Hippuran can be used for such a GFR measurement in conscious spontaneously voiding rats. We found that during intraperitoneal administration, stable plasma levels of 131I-Hippuran could be obtained. However, urinary recovery of 131I-Hippuran was incomplete (66 +/- 32%), leading to a significant overestimation of GFR by 140 +/- 13% in comparison with the GFR measured by the intra-arterial technique. Thus intraperitoneal infusion of renal function tracers cannot replace intra-arterial infusion.

Precision of glomerular filtration rate determinations for long-term slope calculations is improved by simultaneous infusion of 125I-iothalamate and 131I-hippuran.

In studies on the progression of chronic renal failure the measurement of GFR must be very reliable. Sequential determination of GFR using the renal clearances of exogenous tracers such as inulin or iothalamate is the most accepted method. However, because of inaccuracies in urine collection, intratest variation, and thus intertest variation, of these clearances is considerable. This has a negative impact on the precision of long-term slope estimations. A previously described method of GFR determination on the basis of simultaneous infusion of 131I-hippuran and 125I-iothalamate corrects for inaccurate urine collection. To study whether this correction method improves the precision of the GFR slope measurement, this study analyzed longitudinal GFR data obtained in 71 patients with renal disease during a follow-up of 84 to 180 wk (477 renal function studies). All GFR were calculated by using both the standard renal clearance method and the correction method. The intratest and intertest coefficient of variation was significantly smaller for the correction method compared with the standard method (1.93 +/- 0.20 versus 8.48 +/- 1.66% P < 0.0005; and 2.88 +/- 0.32 versus 5.12 +/- 0.66%, P < 0.005, respectively). As a result, the precision of the GFR slope estimation was significantly better with the correction method compared with the standard method (error of the slope, 1.63 +/- 1.09 versus 2.35 +/- 2.36 mL/min per yr, P < 0.01). This improvement in precision of the slope by using the correction method reduces the necessary sample size needed to detect a GFR slope difference between interventions to about 30% of that needed when using the standard method. It is concluded that the precision of GFR measurements is improved by using correction for inaccurate urine collection with concomitant 131I-hippuran clearance.

[Evaluation of renal function using 99mTc-MAG3 comparison with 131I-OIH by simultaneous dual energy peak acquisition method].

A newly developed 99mTc-labeled renal scintigraphic and renographic agent, 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) was studied clinically and compared with 131I-OIH in 16 patients with various renal and urinary tract disorders. The abdominal aorta and the common iliac artery were clearly visualized in the vascular phase. The renogram patterns showed the same pattern in all cases. The parameters on the renogram such as Tmax, T2/3, T1/2 were compared. The highly significant correlations of Tmax, T2/3 and T1/2 were observed between 99mTc-MAG3 and 131I-OIH with correlation coefficient of 0.982, 0.907, 0.990, respectively. In all cases, excretion of 99mTc-MAG3 was slower than that of 131I-OIH and the ratios of Tmax, T2/3 and T1/2 between 99mTc-MAG3 and 131I-OIH were 1.113 +/- 0.121, 1.277 +/- 0.247, 1.179 +/- 0.075, respectively. It is concluded that 99mTc-MAG3 is useful renal imaging agent as an alternative to 131I or 123I-OIH.

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)

Single-dose subcutaneous iodine-131-iodohippurate for determination of renal plasma flow.

Subcutaneous administration of a single dose of 131I-iodohippurate was used for determination of renal plasma flow (RPF) in 20 subjects during water diuresis. Slow release of tracer (200 microCi) permitted serial clearance measurements over 5 hr that were compared to standard, constant infusion, PAH clearance (mean 379.5 +/- 34.9 ml/min/1.73 m2, range 50.9 to 696.3 ml/min/1.73 m2). RPF(Isotope) was 424.9 +/- 30.3 ml/min/1.73 m2 (range 144.4 to 746.5 ml/min/1.73 m2) and highly correlated with RPFPAH (r = 0.883, p less than 0.0001). This technique permits prolonged studies of renal plasma flow under steady-state conditions without constant infusion.

[Clinical evaluation of 123I-orthoiodohippurate (123I-OIH) for diagnosis of renal function: dose finding study].

The safety, clinical usefulness and the optimal dose of 123I-orthoiodohippurate (123I-OIH) were evaluated in patients with mild renal disorders. 123I-OIH was administered intravenously to 45 patients, and 39 of those patients were analyzed for the clinical usefulness. The numbers of cases analyzed were 10 for 9.25 MBq (0.25 mCi), 18.5 MBq (0.5 mCi) and 74 MBq (2.0 mCi) and 9 for 37 MBq (1.0 mCi). Neither adverse reaction nor abnormal laboratory findings due to 123I-OIH administration were observed in the 45 patients. The clinical usefulness of the drug was evaluated in terms of individual renal function, regional renal functions, renal blood flow, parenchymal function and urinary function, and ability to differentiate between the renal and urinary functions, and the overall clinical usefulness. In the evaluation by the investigators, there were no significant differences in each of these parameters among any of the doses administered. In the evaluation by the Committee, however, the usefulness with 74 MBq superior to those with 9.25 MBq and 18.5 MBq, while there was no significant differences between those with 37.5 MBq and 74 MBq. The qualities of the blood flow phase images, functional phase images, functional images, and the statistical noises of the individual and the regional kidney renograms were also evaluated by the Committee. The image qualities and the statistical noises with 37 MBq were superior to those with 9.25 MBq and 18.5 MBq except for the functional image quality, and there were no significant differences between those with 37 MBq and 74 MBq other than the regional renograms and the functional images, which were superior with 74 MBq.(ABSTRACT TRUNCATED AT 250 WORDS)

Deconvolution analysis of renograms obtained with simultaneously administered 99mTc-DTPA and 131I-hippuran.

Seventy patients were studied with a dual radionuclide technique. The conventional renograms and the blood curve were subjected to deconvolution analysis using the matrix algorithm method, and the following curve data calculated from the retention functions: absolute and relative amplitudes, minimum time of the retention function, maximum time of the retention function and mean transit time. The findings with the two radiopharmaceuticals 99mTc-DTPA and 131I-Hippuran were compared under normal and pathological conditions. The correlations between the data with 99mTc-DTPA and those with 131I-Hippuran were highly significant (p less than 0.01). So was the correlation between the absolute amplitude of the retention curve and the rate of uptake based on the corresponding renogram (p less than 0.01). Due to the difference in the renal handling of the two tracers, longer maximum times were obtained with 99mTc-DTPA. The mean transit times were also longer with 99mTc-DTPA, except in kidneys with parenchymal insufficiency. The highest amplitudes were found in normal kidneys, while the lowest values were observed in parenchymal insufficiency. In the group with acute ureteral obstruction, the mean transit times tended to be increased. The maximum times were even more increased. With both tracers it is possible to distinguish between the three groups of renal conditions studied here: Normal, parenchymal insufficiency, and acute ureteral obstruction.

Target organ directed drug delivery: evaluation of renal infusion of chromium-51 ethylenediaminetetraacetate and sodium o-[125I]iodohippurate in the Wistar Kyoto rat.

To evaluate the merits of intrarenal drug delivery, the disposition of chromium-51 ethylenediaminetetraacetate (51Cr EDTA) and sodium o-[125I]iodohippurate (125I OIH) was studied following their constant-rate infusion into either the jugular vein or the left or right renal artery of Wistar Kyoto rats. The contralateral kidney was removed. Renal blood flow through the lateral kidney was measured during the experiment via an electromagnetic flow probe. Urine and systemic arterial blood samples were taken at steady state. The clearance and extraction of both substances by the right kidney were independent of the route of administration. Nonlinear kinetics were observed during infusion of 125I OIH at the highest infusion rate in the left kidney. At steady state the advantage of intrarenal over systemic delivery was limited because of the relative high blood flow of the kidney. Only a small reduction (30%) in systemic concentration was achieved by infusion of 51Cr EDTA. Intrarenal infusion of the lower dose (10 nCi/min) of 125I OIH reduced the systemic concentration by greater than 80% when compared with systemic infusion. Intrarenal infusion of the higher dose (40 nCi/min) saturated elimination processes in parts of the left kidney because of nonhomogeneous flow distribution.

125I-hippuran absorption from the human renal pelvis.

The absorption of 125I-hippuran from human renal pelvis was studied peroperatively in 18 patients with obstruction at the pelviureteric junction. Three types of experiment were included: absorption during induced diuresis, absorption at a constant intrapelvic pressure of 30 cm. H2O, and excretion of the indicator by the contralateral kidney. Total and separate glomerular filtration rate were measured using 51Cr-EDTA clearance technique and isotope renography. Distal tubular function was evaluated as maximum concentration ability. During induced diuresis the intrapelvic pressure increased to an average maximum value of 31.6 cm. H2O. The excretion of isotope from the contralateral kidney varied from one to 44% of the given dose. A significant correlation (r = 0.87) between the maximum intrapelvic pressure obtained and the amount of isotope excreted from the contralateral kidney was demonstrated. At a constant intrapelvic pressure of 30 cm. H2O the excretion of isotope from the contralateral kidney varied from two to 26% of the dosage given. The low value probably depended on the impaired function of the obstructed kidney. Our results show the existence of a significant reflux from the renal pelvis of small molecules, which was affected by renal function, intrapelvic pressure and volume.

Single injection techniques in determining age-related changes in porcine renal function.

Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined in 32 anaesthetised female Large pigs, aged 4-24 months, from the plasma disappearance curves of [99mTc]DTPA and [131I]hippuran respectively. Clearance was also monitored by external counting over the heart. GFR and ERPF increased markedly with age in pigs up to 12 months old, reaching mean values of 242.06 +/- 5.89 and 919.39 +/- 79.01 mL/min. In pigs aged 12-24 months ERPF increased slightly, but renal function remained essentially unchanged after 1 yr of age. These results for renal function were similar to previous estimates, using continuous infusion techniques inferring that GFR and ERPF could be accurately monitored using single injection procedures.

Evaluation of renal function parameters with simultaneously administered 99mTc-DTPA and 131I-hippuran.

The present study aimed at comparing two renal function tests using 99mTc-DTPA (diethylene triamine penta acetic acid) and 131I-labeled hippuran (o-hippuric acid). A mixture of 80 MBq 99mTc-DTPA and 7.4 MBq 131I-hippuran in a total volume of 1.5 ml or less was injected into an arm-vein. Both radiopharmaceuticals have identical initial distributions in the blood pool when injected in this manner. Seventy-two patients were studied with the present dual radionuclide technique. The following parameters were derived from the renogram: area under curve, uptake ratio, Tmax, decrease ratio, excretion ratio, and rate of decrease. The parameters for 99mTc-DTPA and 131I-hippuran were compared for various kidney groups. Generally the renographic parameters were well correlated. Apart from the systematic differences due to different modes of renal excretion, the curve patterns virtually agreed. The differences that were observed between the two tracers lacked clinical significance.

Prediction of urinary excretion of 131I-orthoiodohippurate.

A new formula is presented for the prediction of urinary excretion at approximately 35 min after injection of 131I-orthoiodohippurate, derived from a large series of normal kidney donors, before and after unilateral nephrectomy, and a few patients with diseases in which there was no evidence of urinary tract obstruction. The best formula was: Expected percent dose excretion at 35 min = 79.3[1-e--(0.004798 X ERPF)] with a standard error of estimate (Sy.x) of 5.2% dose. This value has been particularly useful in clinical practice in the calculation of an excretion index (actual/expected percent dose excretion) which separates various post-transplantation entities and various nephrourologic processes.

Use of the double-isotope single-injection method for estimating renal function in normal cross-bred swine.

The double-isotope single-injection method to estimate renal function which utilizes the radiolabeled chemicals [131I]sodium iodohippurate and [125I]sodium iothalamate was evaluated in swine. A total of 46 normal, cross-bred swine were used to determine the applicability of this method for measuring the glomerular filtration rate and effective renal plasma flow. The mean glomerular filtration rate in pigs was determined to be 5.33 +/- 0.82 ml/kg of body weight/minute for [125I]sodium iothalamate with a biological half-life (T 1/2) of 39.18 +/- 7.44 minutes. The mean effective renal plasma flow was determined to be 19.25 +/- 3.12 ml/kg of body weight/minute for [313I]sodium iodohippurate, with a T 1/2 of 18.45 +/- 1.74 minutes. These values are more closely related to the glomerular filtration and effective renal plasma flow values reported for dogs and cats than they are to values reported for man. The method is rapid and reliable; results are available 6 to 8 hours after the experiment. This method is advantageous when information about renal function variables is a prerequisite to pharmacokinetic or toxicologic studies.

Kidney scintigraphy with 99mTc-DMSA and 131I-hippurate.

43 patients underwent an extended scintigraphic procedure with 99mTc-dimercaptosuccinylic acid in order to investigate its proper use for diagnosing morphological and functional kidney abnormalities. The group was comprised of patients without renal disease, and patients with diffuse parenchymal disease, obstructive uropathy, renal cysts and renal tumors. The study was followed by 131I-hippurate renography. We propose a simplified routine procedure with scintiphotos taken 10-15 min after injection for topographic information and 120 min after injection for renal morphology. This procedure allows excellent case finding of diffuse parenchymal disease of a special value in cases of radiological non-visualization. The technique is indicated, when iodine contrast media cannot be used for radiological examinations. DMSA studies, however, do not allow safe functional evaluation in all categories of patients. Neither can obstructive nephropathy be diagnosed unless the renal pelvis is dilated. Renal perfusion studies are contaminated by the perfusion of liver and spleen. Nevertheless, a tentative differentiation between cysts and tumours is possible, the former being hypoperfused the latter hyperperfused. When supplemented with gamma camera 131I-hippurate renography, the total scintigraphic procedure will also include split function determination and run-off evaluation.

[Transport of 131J-iodo-o-hippurate and 22Na out of the retroretinal space in experimental non rhegmatogenous detachment of the retina (author's transl)]. / Abtransport von 131qhippursäure und 22Na aus dem Retroretinal-Raum bei experimenteller arhegmatogener Netzhautablösung

A model of an experimental arhegmatogenous retinal detachment is presented, to allow the measurement of the transport of radioactive labeled substances out of the subretinal space. Experiments were performed on 19 male cats. 131I-iodo-o-hippurate and 22Na were used as test substances. There was no significant difference between the rate of disappearance of 131I-hippurate if injected retroretinally or intravitreally. The rate of disappearance of 131I-hippurate could be slowed down by intravenous infusion of penicillin-G. The rate of disappearance of 22Na following retroretinal injection is not only slower than the rate of disappearance of 22Na injected intravitreally, but significantly slower than the rate of disappearance of 131I-hippurate. For graphic analysis ("curve peeling") of the terms embodied in the curves, more densly situated points of measurements will be necessary. Then the experimental model will serve well to analyze the components influencing the transport of labeled sodium out of the subretinal space.