Long-term changes in renal function and perfusion in heart failure patients with reduced ejection fraction.

INTRODUCTION: Little is known about the natural course of renal function and renal hemodynamics in heart failure patients with reduced ejection fraction (HFREF). METHODS AND RESULTS: We prospectively studied effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) in 73 HFREF patients with (125)I-iothalamate/(131)I-hippuran clearances with a mean follow-up of 34.6 ± 4.4 months. Fifteen percent were female, with age 58 ± 12 years and left ventricular ejection fraction (LVEF) 29 ± 10%. Baseline GFR was 81 ± 23 mL/min/1.73 m(2) and declined 0.6 ± 4.7 mL/min/1.73 m(2) per year. Baseline ERPF was 292 ± 83 mL/min/1.73 m(2) and declined 4.3 ± 19 mL/min/1.73 m(2) per year. Of the baseline variables, older age and high urinary kidney injury molecule-1 were the only variables associated with GFR decline (p < 0.05). Following stepwise backward analysis, only age (p < 0.001) remained significant. In addition, we found an association between change in GFR and changes in ERPF, N-terminal pro-brain natriuretic peptide and renovascular resistance. In the multivariable analysis, only the change in ERPF remained significantly associated with a change in GFR (p < 0.001). CONCLUSION: In this cohort of stable chronic HFREF patients, the average decline in GFR over time was small. The decline of GFR was associated with a higher age and a lower baseline GFR, and was strongly related to changes in renal perfusion.

Monitoring Nonsurgical and Surgical Root Canal Treatment of Teeth with Primary and Secondary Infections

The aim of this study was to monitor nonsurgical and surgical root canal treatment (RCT) of teeth with primary and secondary infections and apical periodontitis (AP). This prospective clinical study comprised the treatment of 80 patients with primary and persistent secondary infections and AP. Of this initial sample, forty patients did not return. Periapical index using cone beam computed tomography scans (CBCTPAI) was used to aid diagnosis, planning and to determine the better therapeutic strategy. Twenty patients (26 teeth) diagnosed with primary infection and AP received conventional RCT and were followed up for 10 to 36 months. Twenty patients (31 teeth) diagnosed with persistent secondary infection were submitted to periapical surgical and followed up for 6 to 30 months. The results showed RCT successful in 19/26 cases with complete AP healing (5/26 with partial repair) in 10-36 months of follow up. For the surgically managed cases, effectiveness of surgical therapy was detected in 10/31 cases with complete healing (10/31 cases with partial repair) within 6-30 months follow up. The return of patients for clinical and radiographic follow-up, and obedience to the proposed time period was very short from ideal. The levels of success in both therapeutic protocols were high. RCT failures were detected even with rigorous standard clinical protocols.

O objetivo do estudo foi monitorar tratamentos de canais radiculares (TCR) convencionais e com auxílio de cirurgia periapical. Este estudo prospectivo constituiu de 80 pacientes portadores de infecções primárias e secundárias persistentes e periodontite apical (PA). O índice periapical utilizando tomografia computadorizada de feixe cônico (CBCTPAI) foi utilizado como auxiliar no diagnóstico, planejamento e para determinar a melhor estratégia terapêutica. Apenas 40 pacientes retornaram para o TCR. Em 20 pacientes (26 dentes) com diagnósticos de infecções primárias e PA foram feitos TCR convencionais e monitoramentos por 10 a 36 meses. Em 20 pacientes (31 dentes) com diagnósticos de infecções secundárias persistentes foram submetidos a procedimentos cirúrgicos e acompanhamentos durante 6 a 30 meses. Os resultados mostraram TCR bem sucedidos em 19 de 26 casos, com curas completas das PA (5 de 26 com reparação parcial) em controles de 10 a 36 meses. Para os casos de tratamentos cirúrgicos foram detectadas eficácias das terapêuticas cirúrgicas em 10 de 31 casos com curas completas (10 de 31 casos com reparação parcial) em controles de 6 a 30 meses. O retorno dos pacientes para controle clínico e radiográfico e a obediência ao período de tempo proposto está muito aquém do ideal. Os níveis de sucesso em ambos os protocolos terapêuticos se mostraram elevados. Fracassos no TCR foram detectados mesmo utilizando protocolo clínico com rigoroso padrão.

99mTc(CO)3(NTA) and 131I-OIH: comparable plasma clearances in patients with chronic kidney disease.

UNLABELLED: The pharmacokinetics of the tricarbonyl core radiopharmaceutical (99m)Tc(CO)3-nitrilotriacetic acid ((99m)Tc(CO)3(NTA)) in rats and subjects with normal renal function are comparable to those of (131)I-o-iodohippuran ((131)I-OIH), the radiopharmaceutical gold standard for the measurement of effective renal plasma flow. Our objective was to compare the pharmacokinetics of these 2 tracers in subjects with renal failure. METHODS: (99m)Tc(CO)3(NTA) was prepared with commercially available NTA and a commercially available labeling kit and isolated by reversed-phase high-performance liquid chromatography. Approximately 74 MBq (2.0 mCi) of (99m)Tc(CO)3(NTA) were coinjected with approximately 11.1 MBq (300 µCi) of (131)I-OIH in 8 subjects with stage 3-4 renal failure; simultaneous images were obtained for 24 min, followed by an anterior image over the gallbladder and abdomen. Plasma clearances were determined from 10 blood samples obtained 3-180 min after injection using the single-injection, 2-compartment model. Plasma protein binding, red cell uptake, and percentage injected dose in the urine at 30 and 180 min were determined. RESULTS: There was no difference in the plasma clearances of (99m)Tc(CO)3(NTA) and (131)I-OIH (177 ± 63 vs. 171 ± 66 mL/min/1.73 m(2), respectively) (P = 0.41). The plasma protein binding and red cell uptake of (99m)Tc(CO)3(NTA) were 35% ± 7% and 6% ± 3%, respectively; both values were significantly lower than the plasma protein binding (71% ± 5%) and red cell uptake (16% ± 2%) of (131)I-OIH (P < 0.001). There was no significant difference in the percentage injected dose in the urine at 30 min (P = 0.24) and at 3 h (P = 0.82); for comparison, the percentage dose in the urine at 3 h was 77% ± 9% for (99m)Tc(CO)3(NTA) and 78% ± 11% for (131)I-OIH. Image quality with (99m)Tc(CO)3(NTA) was excellent and no activity was identified in the gallbladder or intestine. CONCLUSION: Results in patients with renal failure show the clearance and rate of urine excretion of (99m)Tc(CO)3(NTA) to be equivalent to that of (131)I-OIH.

Preclinical evaluation of 99mTc(CO)3-aspartic-N-monoacetic acid, a renal radiotracer with pharmacokinetic properties comparable to 131I-o-iodohippurate.

UNLABELLED: In an ongoing effort to develop a renal tracer with pharmacokinetic properties comparable to p-aminohippurate and superior to those of both (99m)Tc-mercaptoacetyltriglycine and (131)I-o-iodohippurate ((131)I-OIH), we evaluated a new renal tricarbonyl radiotracer based on the aspartic-N-monoacetic acid (ASMA) ligand, (99m)Tc(CO)(3)(ASMA). The ASMA ligand features 2 carboxyl groups and an amine function for the coordination of the {(99m)Tc(CO)(3)}(+) core as well as a dangling carboxylate to facilitate rapid renal clearance. METHODS: rac-ASMA and l-ASMA were labeled with a (99m)Tc-tricarbonyl precursor, and radiochemical purity of the labeled products was determined by high-performance liquid chromatography. Using (131)I-OIH as an internal control, we evaluated biodistribution in normal rats with (99m)Tc(CO)(3)(ASMA) isomers and in rats with renal pedicle ligation with (99m)Tc(CO)(3)(rac-ASMA). Clearance studies were conducted in 4 additional rats. In vitro radiotracer stability was determined in phosphate-buffered saline, pH 7.4, and in challenge studies with cysteine and histidine. (99m)Tc(CO)(3)(ASMA) metabolites in urine were analyzed by high-performance liquid chromatography. RESULTS: Both (99m)Tc(CO)(3)(ASMA) preparations had greater than 99% radiochemical purity and were stable in phosphate-buffered saline, pH 7.4, for 24 h. Challenge studies on both revealed no significant displacement of the ligand. In normal rats, the percentage injected dose in urine at 10 and 60 min for both preparations averaged, respectively, 103% and 106% that of (131)I-OIH. The renal clearances of (99m)Tc(CO)(3)(rac-ASMA) and (131)I-OIH were comparable (P = 0.48). The tracer was excreted unchanged in the urine, proving its in vivo stability. In pedicle-ligated rats, (99m)Tc(CO)(3)(rac-ASMA) had less excretion into the bowel (P < 0.05) than did (131)I-OIH and was better retained in the blood (P < 0.05). CONCLUSION: Both (99m)Tc(CO)(3)(ASMA) complexes have pharmacokinetic properties in rats comparable to or superior to those of (131)I-OIH, and human studies are warranted for their further evaluation.

(99m)Tc(CO)3(NTA): a (99m)Tc renal tracer with pharmacokinetic properties comparable to those of (131)I-OIH in healthy volunteers.

UNLABELLED: Studies in rats showed that the pharmacokinetics of the tricarbonyl core radiopharmaceutical (99m)Tc(CO)(3)-nitrilotriacetic acid, (99m)Tc(CO)(3)(NTA), were essentially identical to those of (131)I ortho-iodohippuran ((131)I-OIH), the clinical gold standard for the measurement of effective renal plasma flow. Our objective was to compare the pharmacokinetics of these 2 tracers in healthy volunteers. METHODS: (99m)Tc(CO)(3)(NTA) was prepared with commercially available NTA and a commercially available kit and isolated by reversed-phase high-performance liquid chromatography. Approximately 74 MBq (2 mCi) of (99m)Tc(CO)(3)(NTA) were coinjected with 9.25 MBq (250 microCi) of (131)I-OIH in 9 volunteers, and simultaneous imaging of each tracer was performed for 24 min. Plasma clearances were determined from 8 blood samples obtained 3-90 min after injection using the single-injection, 2-compartment model. Plasma protein binding, red cell uptake, and percentage injected dose in the urine at 30 and 180 min were determined. RESULTS: There was no difference in the plasma clearances of (99m)Tc(CO)(3)(NTA) and (131)I-OIH, 475 +/- 105 mL/min versus 472 +/- 108 mL/min, respectively. The plasma protein binding and red cell uptake of (99m)Tc(CO)(3)(NTA) were 43% +/- 5% and 9% +/- 6%, respectively; both values were significantly lower (P < 0.001) than the plasma protein binding (75% +/- 3%) and red cell uptake (17% +/- 5%) of (131)I-OIH. There was no significant difference in the percentage injected dose recovered in the urine at 30 min and at 3 h; for comparison, the percentage dose in the urine at 3 h was 91% +/- 4% for (99m)Tc(CO)(3)(NTA) and 91% +/- 6% for (131)I-OIH (P = 0.96). Image quality with (99m)Tc(CO)(3)(NTA) was excellent, and the renogram parameters were similar to those of (131)I-OIH. CONCLUSION: Preliminary results in healthy volunteers suggest that the pharmacokinetic behavior of (99m)Tc(CO)(3)(NTA) is comparable to that of (131)I-OIH.

99mTc(CO)3-nitrilotriacetic acid: a new renal radiopharmaceutical showing pharmacokinetic properties in rats comparable to those of 131I-OIH.

UNLABELLED: To develop a (99m)Tc renal tracer with a capacity to measure effective renal plasma flow comparable to that of the clinical gold standard (131)I-o-iodohippurate ((131)I-OIH) and superior to that of (99m)TcO-mercaptoacetyltriglycine, which has a clearance only 50%-60% that of (131)I-OIH, we investigated (99m)Tc-tricarbonyl nitrilotriacetic acid (Na(2)[(99m)Tc(CO)(3)(NTA)]). This radiopharmaceutical, which is based on an aminopolycarboxylate ligand, is formed as a single species and has a dangling carboxylate group favoring tubular transport. METHODS: Na(2)[(99m)Tc(CO)(3)(NTA)] was prepared by using commercially available NTA and an IsoLink kit and isolated by high-performance liquid chromatography. The stability of Na(2)[(99m)Tc(CO)(3)(NTA)] in isotonic saline was assessed for 24 h and was further evaluated by incubation in 0.1 M cysteine and histidine for 4 h at 37 degrees C. The biodistribution of Na(2)[(99m)Tc(CO)(3)(NTA)], coinjected with (131)I-OIH as an internal control, was evaluated in 5 normal Sprague-Dawley rats at 10 min, 5 normal Sprague-Dawley rats at 60 min (group A), and 6 rats with renal pedicle ligation at 60 min (group B) after injection. Clearance and extraction fraction studies were conducted in 2 normal Sprague-Dawley rats, and urine and plasma from 2 additional normal rats each were analyzed for metabolites by high-performance liquid chromatography. RESULTS: The radiochemical purity of Na(2)[(99m)Tc(CO)(3)(NTA)] was greater than 99%, the complex was stable for 24 h at physiologic pH, and the challenge experiments showed no degradation. In normal rats, the percentage dose in the urine at 10 and 60 min was 108% +/- 9% and 101% +/- 5%, respectively, that of (131)I-OIH; minimal hepatic or gastrointestinal activity was demonstrated. In group B rats, Na(2)[(99m)Tc(CO)(3)(NTA)] was better retained in the blood and had less excretion into the bowel than did (131)I-OIH (P < 0.01). The plasma clearances of Na(2)[(99m)Tc(CO)(3)(NTA)] and (131)I-OIH were comparable, but the extraction fraction of Na(2)[(99m)Tc(CO)(3)(NTA)] was 93.5% +/- 3.8%, compared with 67.9% +/- 6.1% for (131)I-OIH. Plasma protein binding of Na(2)[(99m)Tc(CO)(3)(NTA)] averaged 67% +/- 7%, and red cell uptake was 7% +/- 2%. CONCLUSION: Na(2)[(99m)Tc(CO)(3)(NTA)] is stable, exists as a single species, and has pharmacodynamic properties in rats comparable to those of (131)I-OIH.

Evaluation of (123)I-orthoiodohippurate single kidney clearance rate by renal sequential scintigraphy in a large cohort of likely normal subjects aged between 0 and 18 years.

PURPOSE: Age-related values of (123)I-orthoiodohippurate (OIH) single kidney clearance rate (Cl) were estimated in a large cohort of likely normal children aged between 0 and 18 years. METHODS: Among 4,111 children examined in the past 10 years, 917 were selected with the following inclusion criteria: (a) mild ultrasonographic hydronephrosis with right differential renal function (DRF) <53% and >47% (498 pts), (b) known or suspected urinary tract infection with normal ultrasound, serum creatinine and DMSA and DRF <53% and >47% (419 pts). (123)I-OIH-Cl was assessed using a validated gamma camera method. Children were divided into 21 age classes: from 0 to 2 years, eight 3-month classes; from 2 to 14 years, twelve 1-year classes; from 14 to 18 years, one 4-year class. RESULTS: Cl, plotted against age, was fitted using an increasing function (y=a-be-cx). Mean (123)I-OIH-Cl of 1,834 kidneys was 306+/-22 ml/min/1.73 m(2) BSA. Mean (123)I-OIH-Cl of the right and left kidneys was 307+/-23 and 305+/-22 ml/min/1.73 m(2) BSA, respectively (p<0.002). The best-fitting (123)I-OIH-Cl growing function was: Cl=311-230e-0.69xAge (months). (123)I-OIH-Cl improved progressively starting from birth, reaching 96% and 98% of the mature value at 1 and 1.5 years, respectively. (123)I-OIH-Cl at birth (age=0) was 81 ml/min/1.73 m(2) BSA. After 18.6 days of life, the renal function had doubled its starting value, and it reached a plateau of 311 ml/min/1.73 m(2) BSA at 2 years. CONCLUSION: This work represents a systematic evaluation of ERPF by a gamma camera method in a large cohort of selected likely normal paediatric subjects.

Reassessment of the reproducibility of Technetium-99m mercaptoacetyltriglycine clearance.

BACKGROUND: Conflicting results have been published concerning the reproducibility of Tc-99m MAG3 clearance. The aim of the study was to reevaluate again this reproducibility on a large prospective series of healthy volunteers. MATERIAL AND METHODS: Fifty subjects underwent three successive tests performed at 1-week interval. The physiological conditions were controlled as much as possible and all experimental measurements were rigorously double-checked. Renal clearances were calculated using single sample algorithms. RESULTS: Thin layer chromatography demonstrated a radiochemical purity of more than 92% (mean 93.8%; SD 1.6%; range 92.0-96.4%). The mean (and SD) of 44th minute plasma concentrations for the three successive measurements were respectively 1.8 +/- 0.4, 2.1 +/- 0.4 and 1.9 +/- 0.4 (%dose/liter). The mean changes (and S.D. of differences) between two tests were 0.26 +/- 0.29, -0.08 +/- 0.5 and 0.18 +/- 0.30 respectively between tests 1 and 2, tests 1 and 3, and tests 2 and 3. Using Bubeck's algorithm, the mean clearance values (ml/min/1.73 m2) were 268.8 (range 201.4-336.8), 247.2 (range 170.5-290.3), and 262.8 (range 187.4-340.0) respectively for the first, second and third measurements. Using Russell's approach, the mean clearance values were respectively 314.9 (range: 208.7-441.7), 280.1 (range: 167.5-358.6), and 305.4 (range: 189.5-447.9). CONCLUSIONS: High differences were observed between the 3 tests. Using Russell s formula, the SD of differences between two tests was respectively 35.8, 47.7 and 57.7 ml/min/1.73 m2 between tests 1 and 2, tests 1 and 3, and tests 2 and 3. Whether such a large variability is acceptable in clinical practice depends solely on what the clinician is expecting.

Kinetic parameter estimation from renal measurements with a three-headed SPECT system: a simulation study.

We present here a direct least-squares estimation (DLSE) method for the determination of renal kinetic parameters from sequences of very fast acquisitions performed with a three-headed single photon emission computed tomography (SPECT) system. A simple linear model for the behavior of the radiopharmaceutical, as well as a spatial model for its spatial distribution are defined. The model enables one to estimate the kinetic parameters directly from the projections, once the plasma concentration function is known. A new technique for the accurate reconstruction of time-radioactivity curves based on the direct reconstruction of the region-of-interest contents from a series of data from three-projections is presented. The technique is used to determine the plasma concentration function with a sub-second time resolution. The spatially-variant geometrical response is also included in the model to compensate for the spatial resolution of the SPECT system. Results obtained from simulations are presented. Basic spatial and time features of the simulations are derived from a patient study. Noise and segmentation errors are also simulated. The DLSE method is compared with the conventional one of deriving kinetic parameters from the time series of reconstructed images. The standard deviation of results given by DLSE is less than 2%, whereas with the conventional method it is between 5% and 6%. Within the limit of statistical fluctuations, DLSE results are unbiased whereas those of the conventional method are overestimated by 24%.

Technetium-99m DTPA dimethyl ester: a renal function imaging agent. Comparative studies in animals with technetium-99m mercaptoacetyl triglycine and 131I-ortho-iodohippurate.

The dimethyl ester of diethylene triamine penta-acetic acid (DMDTPA) (I) can be easily and efficiently labelled with 99mTc. This method can be readily adapted for kit formulations to produce a highly stable and very pure chelate, as shown by paper electrophoresis and reverse-phase high performance liquid chromatography experiments. In mice, this chelate was excreted unchanged in the urine, and the amount of renal excretion was much higher than that of 99mTc-DTPA and comparable with that of 99mTc-mercaptoacetyl triglycine (99mTc-MAG(3)) at two different time points. The renal excretion of co-injected 131I-ortho-iodohippurate (131I-OIH), however, was significantly greater than that of the 99mTc chelates. The renal clearance values of 99mTc-DMDTPA and 99mTc-MAG(3) were also similar and exceeded the corresponding value for 99mTc-DTPA, but were only half that of the 131I-OIH value in the rat. The renograms for 99mTc-DMDTPA and 99mTc-MAG(3) showed overall similarity in a dog model. The diethyl ester (III) and monoethyl ester (II) of DTPA, after labelling with 99mTc, produced the same chelate, as shown by analytical results and biological data, indicating that one of the ester groups in the DTPA diester is dealkylated during the chelation procedure. To confirm this, two more ligands, diethylene triamine 1,4,7,7-tetra-acetic acid (IV) and diethylene triamine 1,4,7-triacetic acid (V), were synthesized, resembling DTPA monoalkyl ester (II) and dialkyl ester (I, III), respectively, in the arrangement of the donor atoms. Ligand IV but not ligand V, on 99mTc chelation, can generate the specific pharmacophore for renal tubular transport that is also present in the ester chelates 99mTc-I, 99mTc-II and 99mTc-III, as shown by their decreased renal excretion in mice pretreated with a renal tubular transport inhibitor such as probenecid.

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.

Renal 131I-hippuran extraction in man: effects of dopamine.

AIMS: This study examined the 131I-hippuran extraction fraction during baseline renal blood flow rates and at high flow rates induced by dopamine. METHODS: In 12 healthy subjects, arterial and renal venous sampling was used to measure the renal extraction of 131I-hippuran. Effective renal plasma flow values determined by the urinary clearance of 131I-hippuran were compared with renal plasma flow values corrected for incomplete extraction of 131I-hippuran. RESULTS: Dopamine (3 micro g kg-1 min-1) decreased 131I-hippuran extraction from 75 +/- 4% at baseline to 62 +/- 6% (means +/- 95% confidence intervals, P < 0.001). Hence, the increase in renal plasma flow (85 +/- 23%) greatly exceeded the rise in effective renal plasma flow (51 +/- 15%, P < 0.002). CONCLUSIONS: Dopamine induced increases in renal blood flow are largely under-estimated when measurements are not corrected for incomplete extraction of 131I-hippuran.

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.

How gender and age affect iodine-131-OIH and technetium-99m-MAG3 clearance.

OBJECTIVE: The relationship between age and effective renal plasma flow (ERPF) results, as measured in nuclear medicine, is well known. This paper explores the relationships among gender, age, and ERPF measurements. After reading this paper, the nuclear medicine technologist should be able to: (a) discuss the importance of establishing normal range values for ERPF that include age and gender variables; (b) state how age affects ERPF results; and (c) state how gender affects ERPF results.

Evaluation of effective renal plasma flow with I-127 ortho-iodohippurate and I-123 ortho-iodohippurate in rabbits.

RATIONALE AND OBJECTIVES: Radiolabeled ortho-iodohippurate is commonly employed for evaluating effective renal plasma flow (ERPF) by means of either in vivo scintigraphy and/or plasma clearance curves. A new method has recently been developed for measuring levels of stable iodine (iodine-127) in biologic samples, based on the detection of x-ray fluorescence photons. In this study, the authors assessed the potential of the new system to evaluate ERPF by using an iodinated contrast medium with adequate glomerular filtration and tubular secretion properties. MATERIALS AND METHODS: A commercial system was used to evaluate ERPF after intravenous injection of stable I-127 ortho-iodohippurate. The results were compared with the clearance values of I-123 ortho-iodohippurate, considered the reference standard. Seven rabbits under general anesthesia were given intravenous injections of I-123 ortho-iodohippurate and I-127 ortho-iodohippurate. The corresponding plasma curves were evaluated from 4 to 60 minutes to calculate ERPF as the dose/integral of plasma curve. RESULTS: The initial distribution volumes of I-123 ortho-iodohippurate (149.4 mL/kg +/- 12.1) and I-127 ortho-iodohippurate (148.8 mL/kg +/- 11.8) were virtually superimposable, thus confirming the chemical identity of the two compounds. The plasma clearance values for I-127 ortho-iodohippurate (11.15 mL/min kg(-1) +/- 1.44) were slightly (not significantly) higher than those for I-123 ortho-iodohippurate (10.49 mL/min kg(-1) +/- 1.41), perhaps because of a relative "mass" load effect of the iodinated medium. CONCLUSION: The results obtained in this study demonstrate the feasibility of the new system for evaluating ERPF, provided that a compound with adequate glomerular filtration and tubular secretion properties is employed.

Prediction of renal transplant survival from early postoperative radioisotope studies.

UNLABELLED: It has been routine at the University of Alabama Medical Center to obtain a radionuclide renal function study immediately after transplantation (usually within 3 d) that includes estimation of effective renal plasma flow (ERPF) from a single plasma sample in addition to imaging. We present here the correlation between baseline measurements and the 1-y graft survival. METHODS: Two cohort years were reviewed: 1988, when 131I-orthoiodohippurate (OIH) was used; and 1995, when 99mTc-mercaptoacetyltriglycine (MAG3) was used. ERPF was measured concurrently with gamma-camera imaging by previously published single-injection, single-sample methods (converting MAG3 clearance to ERPF by means of a correction factor). RESULTS: Graft survival during the first postoperative year improved significantly in the interval between cohort years, from 74% of 147 cadaver (CD) grafts in 1988 to 91% of 200 CD grafts in 1995 (log rank test, P < 0.05). In contrast, for living related donor (LRD) grafts there was no significant change, from 91% of 66 in 1988 to 91% of 83 in 1995. The baseline ERPF was a significant predictor of graft survival in both 1988 and 1995 (Wilcoxon test, P > 0.05). For LRD grafts the association was not significant in either year. Using MAG3 (1995), the peak time and the ratio of counting rate (R) at 20 min to that at 3 min (R20:3) were also significant predictors for CD graft survival. Using OIH (1988 cohort), the correlation with peak time did not reach significance, and the R20:3 measurement was not available. Although multivariate combinations (Cox proportional hazards model) did not have significantly more predictive value at the 95% confidence level than ERPF or R20:3 alone, some statisticians suggest a 75% confidence level for adding an additional covariate to a multivariate model. Use of this level led to a model including both ERPF and R20:3. CONCLUSION: Single-sample ERPF measured in the immediate post-transplant period, whether from OIH clearance or MAG3 clearance, was a statistical predictor of graft survival for CD transplants. For MAG3, the peak time and R20:3 were also significant predictors. These associations held only for CD transplants and not for LRD transplants.

Effect of sample number and time on determination of plasma clearance of technetium Tc 99m pentetate and orthoiodohippurate sodium I 131 in dogs and cats.

OBJECTIVE: To determine the effect of number of blood samples and sampling times on plasma clearance of technetium Tc 99m pentetate (Tc99mP) and orthoiodohippurate sodium I 131(OIH). ANIMALS: 20 dogs and 14 cats. PROCEDURE: Plasma clearances of OIH and Tc99mP were calculated by use of a 2-compartment model, on the basis of a 12-point curve as a reference method. Plasma clearance was calculated by use of all possible combinations of 4 to 11 samples. Time schedule yielding the smallest difference from the reference method was considered to be optimal. Regression analysis was performed between the 12-point model and models using a reduced number of samples. RESULTS: SD of the difference between the 12-point clearance and the models with reduced numbers of samples increased when the number of samples decreased. The SD of the difference between 12-point clearance and 4-point clearance was 4.17 ml/min for OIH and 0.94 ml/min for Tc99mP in dogs and 0.45 ml/min for OIH and 0.11 ml/min for Tc99mP in cats. Optimal schedules were distributed logarithmically and included an early sample at 5 or 10 minutes, a late sample at 2.5, 3, 4, or 5 hours for OIH, and a late sample at 4 or 5 hours for Tc99mP. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma clearances of OIH and Tc99mP can be accurately calculated in dogs and cats by use of a single-injection 2-compartment pharmacologic model with a reduced number of blood samples, resulting in an acceptable margin of error.

Simultaneous technetium-99 MAG(3), iodine-131-orthoiodohippurate and iodine-125 iothalamate clearance and biodistribution after bolus injection in rats.

A bolus injection multiple blood sampling method was developed for the simultaneous measurement of blood and plasma clearance of three radiopharmaceuticals in rats. Technetium-99m mercaptoacetyltriglycine ([(99m)Tc]MAG(3)) and iodine-131-orthoiodohippurate ([(131)I]OIH) were used as makers of effective renal blood flow (ERBF), and iodine-125 iothalamate ([(125)I]IOT) was used as a marker of glomerular filtration rate (GFR). These methods can be easily performed in rats without arterial catheterization. Tissue biodistribution was studied in four groups of rats subjected to the following: group A, renal pedicle isolation (sham-operated); group B, ligature of one kidney pedicle; group C, ligature of both renal pedicles; and group D, ligature of both kidney pedicles and the bile duct. Renal clearance of [(99m)Tc]MAG(3) was greater than [(131)I]OIH and both agents were cleared faster than ([(125)I]-IOT). Either of the two markers of ERBF may be used in experimental studies, but it should be borne in mind that these are relative measurements of kidney performance. [(99m)Tc]MAG(3) and [(125)I]-IOT showed bile excretion in healthy rats, so they cannot completely fulfill the requirements for use as markers of ERBF. When renal function was impaired experimentally, [(99m)Tc]MAG(3) and [(125)I]-IOT were excreted in bile and [(131)I]OIH was secreted in the intestine. Thus, while the markers of ERBF and GFR may be reliable under normal physiological conditions, they may give progressively more erroneous values as renal function deteriorates.

Effect of protein binding on renal extraction of 131I-OIH and 99mTc-labeled tubular agents.

UNLABELLED: The clearance of 99mTc-mercaptoacetyltriglycine (MAG3) is less than the clearances of o-131I-iodohippurate (OIH) and 99mTc-labeled DD- and LL-ethylenedicysteine (EC). This difference could be associated with the lower affinity of MAG3 for the tubular transport receptor, but MAG3 is more highly protein bound than OIH and the EC isomers; protein binding could also be an important factor governing tubular extraction. To separate the effects of protein binding from tubular receptor affinity, the extraction fractions (EFs) of MAG3, OIH, and the DD, LL, and DL isomers of 99mTc-EC were measured in an isolated perfused rat kidney model using a protein-free perfusate and perfusates containing bovine serum albumin. METHODS: The right kidney was removed from the rat and perfused with modified Krebs-Henseleit buffers containing 7.5 or 2.5 g/dL bovine serum albumin or a protein-free perfusate. OIH was coinjected into the renal artery with each of the 99mTc-tracers. Protein binding was measured in each of the perfusates, and the venous outflow was collected to determine the EF. RESULTS: The protein binding of MAG3 in the albumin perfusates ranged from 87% to 95%, significantly higher than the 20%-34% range of protein binding observed with the three EC complexes (P < 0.05). In the 2.5 g/dL albumin perfusate, the EF of MAG3 was 44%, significantly less than the 57%-77% EF of the three EC complexes; in the 7.5 g/dL perfusate, the MAG3 EF fell to 18% versus 39%-45% for the EC complexes (P < 0.05). However, in the protein-free perfusate, the EF of MAG3 was 64%, equal to or higher than the 46%-62% EF of the three EC complexes. CONCLUSION: Protein binding modulates the tubular extraction of renal tracers. Protein binding and receptor affinity must be considered in the design of future renal radiopharmaceuticals as well as radiopharmaceuticals targeting other receptors.

Clearance and renal extraction of technetium-99m-L,L-ethylenedicysteine, I-131-ortho-iodohippurate and I-125-iothalamate in pigs.

99mTc-L,L-ethylenedicysteine (99mTc-EC) has been proposed as a 99mTc-labelled alternative to radio-iodinated ortho-iodohippurate (OIH) for renal imaging and evaluation of renal function. The kinetics of this new renal function agent were studied by a single-injection plasma clearance technique in pigs. 99mTc-EC, 131I-OIH and 125I-iothalamate were injected and the plasma concentration of the three tracers was followed for 240 min. Renal, hepatic and total plasma clearance were calculated. There was no difference between the renal plasma clearance of 99mTc-EC and 131I-OIH (175 +/- 9 versus 178 +/- 8 ml min-1, P = 0.43), whereas the difference between the total plasma clearance of 99mTc-EC and 131I-OIH was highly significant (268 +/- 16 versus 185 +/- 9 ml min-1, P = 0.0001). 99mTc-EC had a significant hepatic clearance of 83 +/- 10 ml min-1 whereas the hepatic clearance of 131I-OIH was negligible. Renal plasma extraction of both 99mTc-EC and 131I-OIH decreased significantly between 2 and 240 min post-injection from 0.85 to 0.45% for 99mTc-EC and from 0.93 to 0.57% for 131I-OIH. Red blood cell binding of 99mTc-EC and 131I-OIH was 6.1% and 20%, respectively. The protein binding of 99mTc-EC and 131I-OIH was 32% for both tracers. We conclude that 99mTc-EC is not a suitable tracer for measuring renal function by the single-injection plasma clearance technique in pigs. This is due to a decreasing renal extraction and a significant hepatic clearance.