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 glomerular filtration rate with 99mTc-DTPA: A comparison of gamma camera methods

A comparison has been made between three gamma camera methods for estimation of glomerular filtration rate (GFR) using ^99mTc-DTPA in a group of 27 patients with widely different renal function. Plasma clearance of ^99mTc-DTPA by multiple blood sampling was used as the reference. Percentage uptake of chelate in the bladder and kidneys at 20 min after injection gave the lowest standard error of 8.0 ml/min. Techniques using early uptake of isotope in the kidneys at 2 min after injection gave less accurate estimates. Correction for the vascular activity in the renal region of interest improved the results for the 2 min uptake technique. Gamma camera techniques provide rapid estimates of GFR which are less accurate than those obtained by plasma clearance of labelled chelate.     

Glomerular filtration rate in relation to extracellular fluid volume: Similarity between99mTc-DTPA and inulin

The rate constant ( ₂) of the terminal exponential of the technetium-99m diethylene triamine pentaacetic acid (DTPA) plasma clearance curve is close to the ratio of glomerular filtration rate (GFR) to extracellular fluid volume (ECV) and is therefore a convenient, already normalised, measure of filtration function. Since ₂ depends on the distribution volume of the tracer, our aim was to compare ₂ from inulin and^99mTc-DTPA and also to compare the equilibration kinetics of the two filtration markers. Fifty millititres of^99mTc-DTPA (250 MBq) and inulin (10%), mixed in the same syringe, were given by intravenous injection in 15 patients undergoing routine^99mTc-DTPA renography for a variety of clinical indications. Frequent antecubital venous blood samples were taken up to about 4 h after injection to construct plasma clearance curves from which GFR, ECV and GFR/ECV (i.e. the reciprocal of mean transit time through the distribution volume) were calculated.^99mTc-DTPA/inulin concentration ratio curves were also constructed after normalisation to the ratio in the syringe. GFR given by the two markers correlated closely (DTPA=0.98·inulin—0.4ml/min;r=0.98).^99mTc-DTPA had the same distribution volume as inulin, had a similar transit time through it and gave the same value of ₂ (r=0.98). GFR/ECV from^99mTc-DTPA accordingly correlated closely with GFR/ECV from inulin (DTPA=0.75·inulin+0.99 ml/min;r=0.95). Even though the distribution volumes and the times to equilibration (i.e. to reach the terminal exponential) were similar, the distribution volume of^99mTc-DTPA at about 10 min after injection was, after subtraction of the plasma volume, about twice that of inulin.We confirm the validity of^99mTc-DTPA for measuring GFR. ₂ is a convenient measure of GFR, can be based on the terminal exponential of inulin of^99mTc-DTPA curves and can be converted to GFR/ECV with an appropriate scaling factor. The kinetics or the two clearance curves with respect to anatomical correlates of the exponentials and the rates of diffusion throughout the respective distribution volumes requires further study.     

Renal and extrarenal clearance of99mTc-MAG3: A comparison with125I-OIH and51Cr-EDTA in patients representing all levels of glomerular filtration rate

This investigation was undertaken in order to determine whether the clearance of technetium-99m mercaptoacetyltriglycine (^99mTc-MAG₃) is more closely correlated to the clearance of iodine-125 orthoiodohippurate (¹²⁵I-OIH) than to the clearance of chromium-51 ethylene diamine tetra-acetate (⁵¹Cr-EDTA) and whether there is a clinically significant extrarenal clearance of^99mTc-MAG₃ . Fifty-one patients with a glomerular filtration rate (GFR) of 4–132 ml/min were studied. After a simultaneous single injection of the three tracers, plasma clearance was measured from blood samples 0–5 h post injection (p.i.) (0–24h in patients with GFR<15 ml/min). Renal plasma clearance was measured 0–5 h p.i. The ratio between the renal plasma clearance of^99mTc-MAG₃ and¹²⁵I-OIH was 0.57. The ratio between the renal plasma clearance of^99mTc-MAG₃ and⁵¹Cr-EDTA was 2.57. The coefficient of variation (CV) of the^99mTc-MAG₃/¹²⁵I-OIH ratio was significantly smaller than the CV of the^99mTc-MAG₃/⁵¹Cr-EDTA ratio (13.4% versus 31.2%). The corresponding plasma clearance ratios were 0.59 (CV=14.8%) and 2.48 (CV=27.0%). Plasma clearance overestimated renal plasma clearance by 7.0 ml/min (5.4%) for^99mTc-MAG₃ and by 4.1 ml/min (8.4%) for⁵¹Cr-EDTA. The difference in plasma and renal plasma clearance of¹²⁵I-OIH of 5.5 ml/min did not reach statistical significance. Red blood cell binding of^99mTc-MAG₃,¹²⁵I-OIH and⁵¹Cr-EDTA was 2.0%, 14.6% and 0.2%, respectively. Protein binding of^99mTc-MAG₃,¹²⁵I-OIH and⁵¹Cr-EDTA was 86.3%, 61.1% and 5.9%, respectively. The volume of distribution of^99mTc-MAG₃,¹²⁵I-OIH and⁵¹Cr-EDTA was 16.3%, 27.0% and 19.4% of body weight. In conclusion, the clearances of^99mTc-MAG₃ and¹²⁵I-OIH are more closely correlated than is the clearance of^99mTc-MAG₃ with GFR. Extrarenal clearance of^99mTc-MAG₃ is relatively smaller than extrarenal clearance of⁵¹Cr-EDTA. Thus, plasma clearance of^99mTc-MAG₃ can be used as a measure of renal tubular function.     

The effect of radiopharmaceutical choice on the assessment of the relative renal function in upper urinary tract obstruction

The relative function of the obstructed kidney (RFOK) was assessed in 43 adult patients with upper urinary tract obstruction (UUTO) using ^99mTc-DTPA and ¹³¹I-ortho-iodohippurate (OIH) dynamic studies and ^99mTc-DMSA dynamic and static studies. The patients were divided into five groups according to the duration and degree of obstruction. Findings were as follows: a) in patients with the first occurrence of acute severe obstruction (group 1), the relative glomerular filtration rate (GFR) was significantly less than the relative effective renal plasma flow (ERPF); b) in patients with chronic severe obstruction and long term uroinfection, the relative ERPF decreased significantly compared with the relative GFR; c) the RFOK calculated from the DMSA dynamic study was the same as both the relative GFR or ERPF in any group; d) the RFOK calculated from the DMSA static study seemed to parallel the relative ERPF more closely than the relative GFR, but in group one it was significantly higher than any of three other estimates. It is concluded that ^99mTc-DTPA is the radiopharmaceutical of choice in obstructive uronephropathy, but when interpreting the RFOK, the time course and severity of obstruction, the presence or absence of uroinfection should also be considered.     

99mTc-MAG3: Dynamic studies in patients with renal disease

Animal studies have suggested that ^99mTc-mercapto-acetylglycyl-glycyl-glycine (^99mTc-MAG3) might be suitable for the determination of the renal plasma flow (RPF) because of its high renal clearance. In this study ¹³¹I-orthoiodohippurate (¹³¹I-OIH) and ^99mTc-MAG3 (labeling always >95%) were administered simultaneously in 11 patients (creatinine clearance ranging from 14 to 130 ml/min per 1.73 m²) to measure effective RPF(ERPF) using the standard technique (UV/P). Glomerular filtration rate (GFR; clearance of ¹²⁵I-thalamate, ¹²⁵I-OT) was also measured. The mean ratio of ^99mTc-MAG3 clearance to ¹³¹I-IOH clearance was 0.55±0.02 (SEM), P<0.01, n=16, and was independant of GFR and ERPF. To study this difference in renal handling ofthe radiopharmaceuticals, renal extractions by the right kidney were determined in another six patients after a single shot of the agents. Renal extraction of ^99mTc-MAG3 was 0.60±0.03 after 5 min, and 0.41±0.08 after 30 min. Renal extraction of ¹³¹I-OIH amounted to 0.86±0.04 and 0.77±0.03, respectively. Using renal extractions of 0.41 and 0.77, respectively, it appeared that calculated renal plasma flows measured simultaneously with ^99mTc-MAG3 and ¹³¹I-OIH were similar. Protein binding 30 min after the priming dose was 66% for ^99mTc-MAG3 and 47% for ¹²³I-OIH. We conclude that in spite of a high renal clearance (ratio to ¹²⁵I-OT clearance 2.69±0.27), ^99mTc-MAG3 seems unsuitable for an accurate determination of the RPF. This conclusion is strongly supported bythe observation that the ratio of ^99mTc-MAG3 to ¹³¹I-IOH clearance markedly decreased from 0.66 to 0.32 in a patient with an increase in urinary protein loss.     

Transplant renography: 99m-Tc-DTPA versus 99m-Tc-MAG3. a preliminary note

^99mTc-MAG3 has been proposed as a replacement for both ¹³¹I-hippuran and ^99mTc-DTPA on clinical grounds. We undertook a prospective preliminary study to ascertain whether ^99mTc-MAG3 works better than ^99mTc-DTPA in the follow up of renal transplant recipients. Seventeen patients (21 renograms each MAG3 and DTPA) were studied, together, with a reference group of 10 patients in whom MAG3 and Hippuran clearance rates were determined simultaneously. As expected, ^99mTc-MAG3 analog images were excellent and ^99mTcMAG3 clearance correlated very well with ¹³¹I-hippuran clearance (r=0.978). MAG3 values were 60% of hippuran values. However, when the corresponding renographic and perfusion findings were faced with different diagnostic challenges, such as post transplant renal failure and rejection, ^99mTc MAG3 did not differ from ^99mTc-DTPA in a significant way. ^99mTc-DTPA was superior to ^99mtc-MAG3 in one case of rejection.     

Glomerular filtration rate and the kinetics of 123I-metaiodobenzylguanidine

We have recently reported evidence that the calcium antagonist nifedipine can improve the tumour retention of ¹³¹I-metaiodobenzylguanidine (¹³¹I-MIBG) in patients with malignant phaeochromocytoma. During studies of the pharmacological modification of tumour MIBG kinetics, it is important to distinguish clearly between a direct effect on MIBG cellular retention by a pharmaceutical, and secondary effects due, for example, to a change in glomerular filtration rate (GFR). In order to provide the fundamental kinetic data required for the numerical modelling of the effect of nifedipine on tumour MIBG kinetics, we have investigated the influence of GFR on MIBG plasma and renal kinetics. The ¹²³I-MIBG plasma curve and MIBG renal plasma clearance rate were studied in ten patients, ranging from subjects without biochemical or scintigraphic evidence of phaeochromocytoma to individuals with widely disseminated metastatic disease. GFR was measured using the ^99mTc-DTPA plasma clearance method. In four cases, the studies were repeated with the patients taking oral nifedipine. Statistically significant correlations were found between GFR and the MIBG plasma concentration, MIBG renal plasma clearance rate and the early (0 to 5 min) renal excretion of MIBG. The data permit the evaluation of the plasma integral during the first few min following bolus injection, a quantity important in the numerical modelling of tumour kinetics. GFR was found to have a major influence on whole-body MIBG kinetics, but there was also evidence of the effect of the metastatic tumour burden.     

Estimation of glomerular filtration rate and technetium-99m diethylene triamine penta-acetic acid using chromium-51 ethylene diamine tetra-acetic acid

Simultaneous measurements of the clearance rate of chromium-51 ethylene diamine tetra-acetic acid (⁵¹Cr-EDTA) and technetium-99m diethylene triamine penta-acetic acid (^99mTc-DTPA) were performed in 54 patients with a range of function between 9 and 176 ml/min. Using multiple blood samples the two clearance values correlated well (r = 0.97, SEE 8.6 ml/min) and DTPA clearance was higher by 2.9%. For each radiopharmaceutical the plasma clearance rates obtained using multiple blood samples were compared with those obtained with simplified methods, i.e., the 60–180 min two-sample method of Russell and the mono-exponential method with the Brochner-Mortensen correction. For both radiopharmaceuticals the clearance values correlated well with the Russell method (r = 0.99, SEE = 4.1 ml/min for EDTA;r = 0.99, SEE 4.9 ml/min for DTPA) and the mono-exponential method (r = 0.99, SEE 3.6 ml/min for EDTA;r = 0.99, SEE 3.9 ml/min for DTPA). The mean plasma clearance obtained using multiple blood samples did not differ significantly from that obtained with the Russell method, either in patients with a glomerular filtration rate (GFR)<30 ml/min or in patients with GFR30 ml/min. The mean plasma clearance obtained using multiple blood samples differed significantly from that obtained with the mono-exponential method because of the great difference observed in patients with GFR30 ml/min. It is concluded that the Russell two-sample method after injection of^99mTc-DTPA is accurate enough for routine clinical use.     

Clearance kinetics of solutes used to measure glomerular filtration rate

Agents used to measure glomerular filtration rate (GFR) give a biexponential plasma disappearance curve on multiple peripheral venous sampling between 20 min and 4 h after intravenous injection. These two exponentials are generally regarded to represent equilibration of agent throughout the extracellular fluid (ECF) space and renal clearance, respectively. In seven subjects undergoing diagnostic arteriography, arterial and antecubital venous plasma samples were obtained up to 60 min in five and up to 120 min in two following simultaneous intravenous injection of 99Tcm-diethylene triamine pentaacetate (99Tcm-DTPA) and inulin. The count rate from 99Tcm was simultaneously recorded over the calf with a collimated scintillation probe in five subjects up to 60 min post-injection. The arterial and venous time-concentration curves were interpolated and subtracted to give a curve of the arterio-venous (A-V) concentration difference, which was then integrated. Arterial time-concentration curves display three exponentials, the first of which has the largest amplitude and disappears by about 20 min. The A-V concentration difference becomes zero at about the same time. The integral of the A-V concentration difference, which represents activity in the interstitial space of the forearm, has a time course consistent with the second compartment of a model of two compartments in series (the first being plasma) and a time course that is reciprocally similar to the first exponential of the triexponential arterial plasma curve. The curve externally recorded by scintillation probe has a shape consistent with a signal that is the composite of interstitial 99Tcm-DTPA and plasma 99Tcm-DTPA activities. The arterial plasma clearance curve of GFR agents is triexponential; the first exponential reflects equilibration of agent between plasma and the interstitial space of carcass tissue (mainly muscle and skin). The second exponential is minor compared with the first; it is not clear what it represents. The third exponential reflects renal clearance.     

Different kinetics of lung clearance of technetium-99m labelled diethylene triamine penta-acetic acid in patients with sarcoidosis and smokers

The rate of clearance from the lungs of inhaled technetium-99m labelled diethylene triamine penta-acetic acid (^99mTc-DTPA) is often increased in interstitial lung disease as well as in smoking. In smokers a bi-exponential clearance course of ⁹⁹mTc-DTPA when measured over 3 h has previously been shown. This study was performed to compare the kinetics of clearance of ^99mTc-DTPA, measured for 3 h, in sarcoid patients and healthy smokers. Forty-one never-smoking patients with sarcoidosis and radiological signs of intrathoracic disease were studied. The results were compared with those of 16 healthy current smokers and of 14 healthy never-smokers reported previously. A mono-exponential clearance equation described the clearance in 22 of the sarcoid patients and all normal never-smokers, but with a shorter average tracer half-life in the patients (P<0.05). In 19 patients and all smokers a bi-exponential equation gave a significantly better curve fit. The rate of clearance of the slow component was higher in patients with sarcoidosis than in smokers (P< 0.05). The fraction of the tracer cleared by the fast clearance component was smaller in patients with sarcoidosis than in smokers (P<0.01). Differences in kinetics of clearance of ^99mTc-DTPA in sarcoidosis and smoking could thus be demonstrated, suggesting that the abnormal clearance is caused by diverging pathophysiological mechanisms.     

Comparative investigations of renal scanning agents

A comparison was made of the biologic behavior of the following radiopharmaceuticals for use in cases of renal disease: ¹³¹I-Hippuran, ¹⁹⁷Hg-chlormerodrin, ^99mTc-DTPA(Sn), ^99mTc-glucono-galactogluconate-calcium(Sn). Biologic investigations included determining the organ distribution, the blood, liver, kidney, and urine clearances, and the whole body retention of the radiopharmaceuticals after intravenous injection in normal Wistar rats. Clinical investigation of the usefulness of these labeled compounds was performed in 32 patients with different nephrologic and urologic kidney diseases. For better evaluation of the tracers, two were administered simultaneously, in the following combinations: ¹⁹⁷Hg-chlormerodrin and ¹³¹I-Hippuraan, ¹⁹⁷Hg-chlormerodrin and ^99mTc-DTPA(Sn) or ^99mTc-DTPA(Fe), ¹⁹⁷Hg-chlormerodrin and ^99mTc-Fe-ascorbic acid, ¹⁹⁷Hg-chlormerodrin and ^99mTc-gluconate, and ^99mTc-gluconate and ^99mTc-Fe-ascorbic acid. The results show that the chelates DTPA(Sn) and DTPA(Fe) labeled with ^99mTc are very useful in static and dynamic investigations of kidney function and morphology, and that ^99mTc-Fe-ascorbic acid and ^99mTc-gluconate are very useful for the study of kidney morphology. The superiority of these preparations over ¹³¹I-Hippuran and ¹⁹⁷Hg-chlormerodrin was evident above all in cases of renal failure and radiologically silent kidney.     

99mTc-aprotinin: A new tracer for kidney morphology and function

Aprotinin (Ap), a low-molecular-weight polypeptide (6500 dalton), is a protease inhibitor which is electively and stably accumulated in the kidney. In 112 adult patients, with either uni- or bilateral renal disease with different degrees of renal impairment (from normal GFR to advanced renal failure), renal scans were performed by means of Ap labelled with^99mTc. Highly satisfactory renal scans were obtained in all patients. In 20 patients with renal failure (serum creatinine 1.8–8.5 mg/dl, mean 4.7) a comparison was made of the renal scans obtained with^99mTc-Ap and with^99mTc-DMSA.^99mTc-Ap was slightly better than^99mTc-DMSA, especially in patients with far advanced renal failure.Some aspects of the pharmacokinetics of^99mTc-Ap were studied in 72 cases. In 22 of these patients plasma clearance of^99mTc-Ap was determined by the single injection method using a two-compartment model. In patients with GFR>90 ml/min plasma clearance of^99mTc-Ap was 67.6±8.4 SD ml/min. A good correlation was observed between plasma clearance of^99mTc-Ap and GFR (r=0.74). After IV injection^99mTc-Ap was stably fixed by the kidney. Renal radioactivity remained stable between the second and eighth hour after the injection. Urinary excretion of radioactivity measured in 35 patients in the first and in the second 2-h interval after IV injection of^99mTc-Ap was negligible in all patients (2.7±1.5 SD percent of the dose in the first 2 h; 2.8±1.4 SD between the second and fourth hour). ^99mTc-Ap is an excellent agent for renal imaging. It also seems promising for renal function studies.     

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)ldt, 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 [ · LV(0)], where 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 a 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/1 [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^99mTcDTPA study. They also correlated significantly with the plasma cyclosporin trough level in 14 patients with dermatomyositis on the 30 occasions when this measurement was made within 1 week of the renogram (r = –0.38,P < 0.05 for GFR/PV andr = –0.77,P < 0.001 for GFR/ECV). The ratio of GFR/PV to GFR/ECV is the ratio of extracellular fluid volume to plasma volume, and this was 4.0 (SD 0.99). We conclude that both GFR/PV and GFR/ECV can be easily measured with^99mTc-DTPA and are physiologically valid expressions of GFR. Although GFR/PV and GFR/ECV correlate with each other, the question is raised as to which of the two fluid volumes is the most appropriate for normalising GFR. Correspondence to: A.M. Peters     

Comparison of methods for determination of glomerular filtration rate: Tc-99m-DTPA renography, predicted creatinine clearance method and plasma sample method

Background: The gamma camera uptake method with Tc-99m-DTPA is simple and less time consuming for the determination of the glomerular filtration rate (GFR). However, its diagnostic accuracy is debated. Gates’ method and predicted creatinine clearance method were compared with plasma clearance method with Tc-99m-DTPA for the measurement of GFR.Materials and Methods: Tc-99m-DTPA renography was performed on 133 patients (69 males and 64 females; age range being 24 to 84 years) with a wide range of renal function. The GFR was determined simultaneously by 3 methods; (1) gamma camera uptake method (modified Gates, Gates); (2) predicted creatinine clearance method (Cockcroft-Gault, CG); (3) single- or two-plasma clearance method (plasma sample clearance method, PSC). The PSC was chosen as a reference.Results: The regression equation of the Gates and the CG against the PSC wasY=11.89 + 1.041X (r=0.790, p<0.001, RMSE=23.55 ml/min/1.73 m²) andY=8.845+0.7899X (r=0.8270, p<0.001, RMSE =16.27 ml/min/1.73 m²), respectively. In comparison with the GFR by PSC, the Gates tended to everestimate the GFR, and contrarily the CG tended to underestimate the GFR.Conclusion: The Gates correlates well with the PSC. However, the Gates is even less precise than the CG. The Gates’ method in Tc-99m-DTPA renography is not suitable for the estimation of GFR in routine practice.     

Technetium-99mL,l-ethylenedicysteine clearance and correlation with iodine-125 orthoiodohippurate for the determination of effective renal plasma flow

Technetium-99mL,l-ethylenedicysteine (^99mTcL,l-EC) is a new renal tubular tracer that allows the determination of the effective renal plasma flow (ERPF). The aim of this study was to derive simplified methods for the estimation of^99mTc-L,l-EC clearance using one or two plasma samples after bolus injection. Fifty-nine multiple plasma dual-tracer samples (nine samples from 5 to 120 min after injection) were obtained after injection of kit-formulated^99mTc-L,l-EC and iodine-125 orthoiodohippurate (01H). The studies were performed in 25 stable and 24 unstable transplant recipients, in five patients with renal insufficiency (four on chronic haemodialysis) and in five normal volunteers. This allowed a wide range of renal function values to be covered, with ERPF (estimated by 01H clearance) ranging from 25.4 to 604.0 ml/min. The reference^99mTc-L,l-EC clearance, as calculated from the multisample model, could be estimated from two samples at 15 and 90 min with an error of 11.3 ml/min and from one sample at 90 min with an error of 17.8 ml/min. Using appropriate linear regression analysis, ERPF could be estimated by the two- and one sample^99mTc-L,l-EC clearance with an error of 24.2 and 22.8 ml/min, respectively. In conclusion,^99mTc-L,l-EC clearance can be accurately estimated by simplified one or two-sample methods. Moreover, these methods can be used to estimate ERPF with an error that remains acceptable for clinical purposes.     

Accurate assessment of long-term nephrotoxicity after peptide receptor radionuclide therapy with 177Lu-octreotate

Purpose

Renal radiation during peptide receptor radionuclide therapy (PRRT) may result in glomerular damage, a potential reduction of glomerular filtration rate (GFR) and ultimately lead to renal failure. While reported PRRT nephrotoxicity is limited to data derived from serum creatinine—allowing only approximate estimates of GFR—the aim of this study is to accurately determine PRRT-induced long-term changes of renal function and associated risk factors according to state-of-the-art GFR measurement.

Methods

Nephrotoxicity was analysed using ^99mTc-diethylenetriaminepentaacetic acid (DTPA) clearance data of 74 consecutive patients with gastroenteropancreatic neuroendocrine tumours (GEP NET) undergoing PRRT with ¹⁷⁷Lu-octreotate. The mean follow-up period was 21 months (range 12–50) with a median of five GFR measurements per patient. The change of GFR was analysed by linear curve fit. Potential risk factors including diabetes mellitus, arterial hypertension, previous chemotherapy, renal impairment at baseline and cumulative administered activity were analysed regarding potential impact on renal function loss. In addition, Common Terminology Criteria for Adverse Events (CTCAE) v3.0 were used to compare nephrotoxicity determined by ^99mTc-DTPA clearance versus serum creatinine.

Results

The alteration in GFR differed widely among the patients (mean ?2.1?±?13.1 ml/min/m² per year, relative yearly reduction ?1.8?±?18.9 %). Fifteen patients (21 %) experienced a mild (2–10 ml/min/m² per year) and 16 patients (22 %) a significant (>10 ml/min/m² per year) decline of GFR following PRRT. However, 11 patients (15 %) showed an increase of >10 ml/min/m² per year. Relevant nephrotoxicity according to CTCAE (grade ≥3) was observed in one patient (1.3 %) with arterial hypertension and history of chemotherapy. Nephrotoxicity according to serum creatinine was discordant to that defined by GFR in 15 % of the assessments and led to underestimation in 12 % of patients. None of the investigated factors including cumulative administered activity contributed to the decline of renal function.

Conclusion

Serious nephrotoxicity after PRRT with ¹⁷⁷Lu-octreotate is rare (1.3 %). However, slight renal impairment (GFR loss >2 ml/min/m² per year) can frequently (43 %) be detected by ^99mTc-DTPA clearance assessments. Cumulative administered activity of ¹⁷⁷Lu-octreotate is not a major determinant of renal impairment in our study.     

Assessment of alveolar epithelial permeability in Behçet’s disease with <Superscript>99m</Superscript>Tc-DTPA aerosol scintigraphy

Objective

Behçet’s disease (BD) is a multisystem disorder characterized by vasculitis, and consists of a triad of recurrent ulcers of the oral and genital mucosa with relapsing uveitis. The prevalance of pulmonary involvement varies in the range of 1–10% in various studies and its complications are severe and life threatening. In this study, we investigated the changes of pulmonary epithelial permeability of patients with BD using technetium-99m diethylene triamine penta-acetic acid (^99mTc-DTPA) aerosol scintigraphy, so as to begin the therapy regimen as soon as possible.

Methods

Twenty-one nonsmoking patients with BD (8 women, 13 men; mean age 38.67 ± 8.86 years) and 15 healthy volunteer nonsmoking controls (8 women, 7 men; mean age 50.87 ± 12.45 years) underwent ^99mTc-DTPA aerosol inhalation scintigraphy and pulmonary function tests (PFTs). Subjects inhaled 1480 MBq of ^99mTc-DTPA for 4 min in the supine position. Scintigraphic data were recorded dynamically (1 frame/min) in the posterior projection on a 64 × 64 matrix for a 30-min period using a double-headed gamma camera (Infinia, GE, Tirat Hacarmel, Israel) equipped with a low-energy all-purpose parallel hole collimator. Half time of ^99mTc-DTPA clearance (T _1/2) was calculated by placing a mono-exponential fit on the curves. Penetration index (PI) was also calculated by dividing the peripheral total counts by the sum of the peripheral and central total counts on the first minute image, in order to quantify the distribution of the inhaled aerosol.

Results

The clearance half time of ^99mTc-DTPA radioaerosols in the BD patients (24.81 ± 6.22 min) was faster than in the normal control group (46.53 ± 22.41 min) (P = 0.004). There was also a significant difference between PI of the patients with BD (0.15 ± 0.03) and that of the controls (0.21 ± 0.06) (P = 0.002). No correlation was found between the mean T _1/2 values of ^99mTc-DTPA clearance or the spirometric measurements in the BD patients. Penetration indices were not correlated with PFT in the BD patients.

Conclusions

Lung epithelial permeability of the patients with BD was significantly higher than that of the normal subjects. The results of this study demonstrated that the assessment of lung epithelial permeability using ^99mTc-DTPA aerosol scintigraphy could predict the presence of lung involvement in the early stages of BD.

     

Potential use of iodine-123 metaiodobenzylguanidine radioaerosol as a marker of pulmonary neuroadrenergic function

Iodine-123 metaiodobenzylguanidine (¹²³IMIBG) radioaerosol is of potential use in the investigation of the neuroadrenergic function of the lungs; however, before the method can be successfully employed the following issues need to be clarified: (1) Does the nebulization affect the radiochemical purity of¹²³IMIBG? (2) Is the pulmonary distribution of inhaled¹²³IMIBG homogeneous in normal subjects? (3) Does the pulmonary clearance of inhaled¹²³I-MIBG reflect the functional status of the neuroadrenergic system of the lungs? In this study we performed: (1) a chromatographic study of nebulized¹²³I-MIBG; (2) a quantitative evaluation of the lung distribution of¹²³I-MIBG radioaerosol in normal subjects as compared with that of technetium-99m diethylene triamine penta-acetic acid (^99mTc-DTPA) and (3) an assessment of¹²³I-MIBG lung clearance both under control conditions and after pharmacologically induced beta-blockade, again compared with^99mTc-DTPA. For these purposes, eight normal subjects were divided randomly into an “MIBG group” and a “DTPA group” (four subjects each) and submitted to three scintigraphic studies each: a baseline study, and studies after the administration of a low (80 mg) and a high (160 mg) dose of propranolol. Radiochemical purity of nebulized¹²³IMIBG ranged between 97.18% and 98.70%. The lung distribution of¹²³I-MIBG, as judged by the aerosol penetration index, was identical to that of^99mTc-DTPA under all study conditions. The¹²³I-MIBG clearance rate was slower than that of^99mTc-DTPA under baseline conditions (135±32 min vs 69±27 min,P<0.01) and increased significantly after propranolol administrations, while the^99mTc-DTPA clearance did not change. The following conclusions were drawn: (1) the nebulization does not affect the radiochemical purity of¹²³I-MIBG; (2) the lung distribution of¹²³I-MIBG is homogeneous in normal subjects; (3) the pulmonary clearance of¹²³IMIBG reflects the functional status of the neuroadrenergic system of the lungs. Thus this scintigraphic method is suitable for research and perhaps for future clinical use.     

Simplified estimation of glomerular filtration rate and effective renal plasma flow

A method is described for the determination of GFR and ERPF using a combined injection of ⁵¹Cr-EDTA and ¹²⁵I-iodohippurate. Plasma samples obtained at 60 min and 150 min after administration were used to determine a flow rate F assuming a monoexponential clearance of the tracers. Empirical relationships were found between F and the true GFR and ERPF determined from multiple sampling and multi-exponential analysis of the clearance curves. The method was shown to be superior to previously published methods involving one or two samples. GRF was calculated with a standard deviation (SD) of only 3.3 ml/min when compared to the multiple sample technique (the reference method), whereas the best estimate from a single sample had a SD of 6.3 ml/min. An improvement in accuracy of ERPF estimation was achieved for values of flow of less than 200 ml/min when the SD was only 9.3 ml/min.