Kidney function after radical nephrectomy: assessment by quantitative SPECT of 99mTc-DMSA uptake by the kidneys.

To determine the function of the remaining contralateral kidney after the removal of a functioning kidney, 30 consecutive patients (18 men, 12 women; average age, 67 y; age range, 34-87 y) who were undergoing unilateral radical nephrectomy were evaluated by sequential quantitative 99mTc-dimercaptosuccinic acid (DMSA) SPECT (QDMSA) studies. METHODS: The 30 patients were undergoing radical nephrectomy for renal tumors. The first study was done before surgery. Follow-up studies were performed 2-23 mo after surgery. Clinical evaluations and determinations of serum creatinine level were performed at the same time as the QDMSA studies. RESULTS: The relative contribution of the resected kidneys to the global renal function before surgery was 43.2% +/- 7.3%. After surgery the uptake of the remaining kidney increased from 13.4% +/- 4.0% to 18.3% +/- 5.8% (t = 5.7; P = 0.0000). The relative function of the remaining kidney increased from 56.8% +/- 7.1% to 79.1% +/- 23.6% (t = 4.9; P < 0.0001) of the global renal function before nephrectomy. Increases in the renal volume (from 211 +/- 62 cm3 to 229 +/- 68 cm3; t = 4.5; P = 0.0001) and in the percentage injected dose per cubic centimeter (%ID/cm3) of the remaining kidney (from 0.066 +/- 0.02 % ID/cm3 to 0.085 +/- 0.03 %ID/cm3; t = 4.6; P = 0.0001) were associated with this change. Nine patients had 2 follow-up studies performed 3-4 mo after surgery and 12-14 mo after surgery. The volume of the remaining kidney (209.22 +/- 46.20 cm3 versus 217.88 +/- 58.85 cm3; t = 0.962; P = 0.364), the %ID/cm3 (0.09 +/- 0.016 %ID/cm3 versus 0.093 +/- 0.025 %ID/cm3; t = 0.362; P = 0.726), and the percentage uptake (19.26% +/- 4.45% versus 20.11% +/- 7.01%) did not change significantly between these 2 QDMSA studies. CONCLUSION: The results of this study suggest that adaptive changes causing hyperfunction of the remaining kidney may occur after nephrectomy of a functioning kidney in adults. These changes occur soon after surgery, persist for at least 1 y, and are evident on QDMSA studies.     

Quantitative SPECT of 99mTc-DMSA uptake in kidneys of infants with unilateral ureteropelvic junction obstruction: assessment of structural and functional abnormalities.

We evaluated individual renal function using quantitative SPECT of dimercaptosuccinic acid (DMSA) uptake by the kidneys (QDMSA) in infants with unilateral ureteropelvic junction (UPJ) obstruction and compared our findings with infants without obstruction. METHODS: QDMSA was performed on 13 infants (mean age of 2.8 +/- 2.8 mo) with unilateral UPJ obstruction and on 15 age-matched controls without obstruction. RESULTS: Control kidneys (n = 30) had a volume of 43.5 +/- 8.8 mL, a percentage injected dose (%ID)/mL 0.62 +/- 0.12 and uptake of 26.1% +/- 3.9%. Kidneys with UPJ obstruction (n = 13) had a volume of 61.2 +/- 19.3 mL, a %ID/mL of 0.42 +/- 0.11 and uptake of 25.4% +/- 8.2%. Contralateral kidneys (n = 13) had a volume of 44.0 +/- 11.9 mL, a %ID/mL of 0.57 +/- 0.16 and uptake of 24.2% +/- 4.6%. The uptake in obstructed kidneys was similar to that observed in contralateral and control kidneys (t = -0.77, P = 0.45; t = -0.37, P = 0.71; respectively). UPJ kidneys had a statistically significant increased volume and decreased %ID/mL, compared with contralateral kidneys (t = 3.35, P < 0.006 and t = 3.75, P < 0.003, respectively) and control kidneys (t = -4.2, P < 0.001 and t = 4.7, P < 0.001, respectively). There was no significant difference between contralateral kidneys and control kidneys regarding volume (t = -0.16, P = 0.87), %ID/mL (t = 0.98, P = 0.33) and uptake (t = -1.41, P = 0.16). Of 13 infants, 11 (85%) showed large kidneys with thinning of the renal cortex. In 1 infant, there was no difference between the obstructed and contralateral kidneys regarding volume, %ID/mL and uptake, and 1 infant showed significant decreased uptake in the UPJ kidney compared with the contralateral kidney. CONCLUSION: Although the overall renal function of the obstructed kidneys remained unchanged, there was a statistically significant decrease in the %ID/mL of renal tissue in UPJ kidneys, which may represent renal dysfunction. Increased functional volume with a thin cortex may represent a compensatory mechanism of the obstructed kidney. Such changes may contribute to the understanding of pathophysiologic mechanisms and may be an early sign of obstruction in infants with hydronephrosis. Further longitudinal studies with an extended number of infants and serial measurements of kidney volumes and %ID/mL are warranted to assess the significance of QDMSA in the management of infants with asymptomatic unilateral renal pelvic dilatation.     

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 greater than 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 less than 0.01, n = 16, and was independent of GFR and ERPF. To study this difference in renal handling of the 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.(ABSTRACT TRUNCATED AT 250 WORDS)     

The half maximum time of (99m)Tc-DTPA renography measured in healthy kidney donors, compared to (131)I-OIH

Technetium-99m-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) has been widely used after (131)I-ortho-hippurate ((131)I-OIH) for renography and to test renal function. Only a few reports refer to normal values range of (99m)Tc-DTPA renography half maximum time (HMT). We have measured the normal value range of (99m)Tc-DTPA renography HMT in our department, of 433 healthy kidney donors from 2007 to 2010, and compared these results with those of (131)I-OIH renography. There were 326 men and 107 women, 18y-69y (median age 29y), subjects were measured before the donation of their kidneys operation and their biochemical, ultrasound and renal function tests were normal. All subjects drunk at least 1 litre of tap water before renography. The (99m)Tc-DTPA dynamic scintigraphy was performed in the posterior view by injecting intravenously as a bolus 185-296MBq. Dynamic imaging was performed immediately after the injection, using a high-resolution low-energy general purpose collimator and a large field of view dual-detector gamma-camera (Hawkeye; General Electric Medical Systems, USA). Matrix was 64Χ64, the phase acquisition time of blood perfusion was 1s/frame and 30 frames were collected. Dynamic acquisition was 30s/frame and 39 frames were collected. Total acquisition time was 20min. We defined as background two regions of interest around the kidneys and the aorta, for radioactive decay correction. We also compared (99m)Tc-DTPA renography HMT values with the HMT values of (131)I-OIH, between the two kidneys, and between men and women. The findings were evaluated by using frequency distribution analysis, paired Sample Student's t-test and one sample t test, with a level of significance P<0.05. We used the SPSS 10.0 statistical software. Since values beyond a high boundary were regarded as unusual, we used the P(95), i.e. " 95% of HMT reference ranges value" to determine the medical reference range of values, as the HMT normal limit. This reference value is used especially when the data shows a skewed distribution. For the HMT (P(95) value), the normal reference values found between mean values of the left and the right kidney were: 10.76±4.14min and 10.89±4.55min, respectively and P=0.416, two tailed. For the left kidney HMT, there was no significant difference between men: 10.90±4.31min and women: 10.33±3.57min, (t=1.235, v=432, P=0.2186, two tailed), and similar findings were found between men's right kidney HMT: 11.02±4.89min and women's right kidney HMT: 10.49±3.32min, (t=1.253, v=266.59, P=0.211, two tailed). By comparing the mean value of (99m)Tc-DTPA renography HMT measured (10.76min, 10.89min) with the mean value of (131)I renography HMT that we found in the literature as referring to both left and right kidneys (4min). We found a significant difference (P=0.000, two tailed). Renography may be used to diagnose urinary tract obstruction, estimate the split renal function and is useful.     

Renal function after tumor enucleation: assessment by quantitative SPECT of 99mTc-dimercaptosuccinic acid uptake by the kidneys.

The purpose of this study was to evaluate the amount of functioning renal mass removed and the amount of remaining individual renal function after tumor enucleation. METHODS: Renal functional volume, percentage injected dose (%ID) per cubic centimeter of renal tissue and individual renal uptake of 24 operated and 24 contralateral kidneys were studied by two sequential SPECT quantitations of 99mTc-dimercaptosuccinic acid (DMSA) uptake by the kidneys (QDMSA). The first study was before surgery and the second study was 1 to 6 mo (mean 3.5 mo) after surgery. Mean tumor size was 3.4 +/- 0.99 cm and all tumors were confined to the renal parenchyma (stages pT1 and pT2). RESULTS: In the operated kidneys, there was a statistically significant decrease in renal cortical volume (170 +/- 46 mL after surgery versus 207 +/- 45 mL before surgery, t = 6.2, P < 0.001) and individual renal uptake (10.3% +/- 3.0% after surgery versus 13.0% +/- 2.9% before surgery, t = 5.4, P < 0.001). There was no statistically significant change after surgery compared with before surgery in the %ID per cubic centimeter of renal tissue of the operated kidneys, and in the volume, %ID per cubic centimeter and uptake of the contralateral normal kidneys. CONCLUSION: The results suggest that QDMSA is a noninvasive method able to assess changes in separate renal function. The limited functioning parenchymal loss after tumor enucleation had no effect on the opposite kidneys.     

Quantitative evaluation of iodine-123 hippuran gamma camera renography in normal children

In a retrospective study of 39 normal children submitted to [123I]hippuran gamma camera renography, a quantitative evaluation of the recorded data showed that: (a) the rate constant for renal plasma clearance of [123I]hippuran was -0.166 +/- 0.043 min-1 corresponding to a hippuran plasma clearance of 518 +/- 142 ml/min per 1.73 m2; (b) the fractional renal clearance of [123I]hippuran was 0.51 +/- 0.03 and 0.49 +/- 0.03 for the left and the right kidney, respectively; and (c) the mean values for the mean transit times of [123I]hippuran through the whole kidney, the renal parenchyma, and the renal pelvis, respectively, were 4.2, 1.9, and 2.5 min. Five kidneys (in four patients) showed prolonged renal mean transit times of [123I]hippuran. Follow-up renographies were performed in three of the four children and gave normal results. Patients with renal mean transit times above the present 5% significance limit of 8.2 min should not necessarily be considered having an abnormal renal function.     

F+0 diuresis renography in infants and children.

The purpose of this study was to evaluate the feasibility of modifying diuresis renography by the simultaneous administration of 99mTc-mercaptoacetyltriglycine (MAG3) and furosemide in the investigation of hydronephrosis and hydroureteronephrosis in infants and children. Two parameters were assessed: the diuretic response in normal kidneys and the ability of the F+0 study to differentiate between renal obstruction and nonobstruction and to identify the level of obstruction in cases of renal obstruction. METHODS: Seventy-two patients (48 males, 24 females; age 2 d to 7 y; median age 6 wk) with sonographic diagnoses of hydronephrosis or hydroureteronephrosis were reviewed prospectively over a 3-y period. All patients had prior sonographic studies and micturating cystourethrography. Bladder catheterization was not routinely performed and was undertaken only if the child had suspected vesicoureteric junction (VUJ) obstruction or grade II or more vesicoureteric reflux. A weight-adjusted dose of 99mTc-MAG3 (maximum 200 MBq, minimum 20 MBq) and 1 mg/kg of furosemide (maximum 40 mg) were administered intravenously at the same time. Posterior imaging of the kidneys and bladder was performed for 20 min and followed by gravity-assisted drainage or imaging after voiding. All patients were followed-up for 6-12 mo, and the final diagnoses were based on either surgery or conservative management with repeated sonography or follow-up 99mTc-MAG3 studies (or both). The results of the F+0 diuresis renography were then compared with the final diagnoses. RESULTS: A renal unit was defined as a kidney and its ureter. There were 151 renal units with 1 patient having bilateral duplex kidneys, 6 patients having unilateral duplex kidneys and 1 patient having a solitary kidney. Fifty-five normal renal units and 96 abnormal renal units on the basis of sonographic findings were assessed. The furosemide clearance half-time for the 55 normal renal units was 1.3-6.3 min (mean 3.8 min). Of the 96 abnormal renal units, 53 were classified as nonobstructed and 43 were classified as obstructed. Of the 53 renal units classified as nonobstructed, there were 48 true-negative studies and 5 false-negative studies; of the 43 renal units classified as obstructed, there were 40 true-positive studies and 3 false-positive studies. The sensitivity was 88.9%, specificity was 94.1% and accuracy was 91.7%. The level of obstruction, either pelviureteric junction or VUJ, was also correctly identified. CONCLUSION: F+0 diuresis renography shows excellent diuretic responses in normal kidneys and is a valid method for the investigation of hydronephrosis and hydroureteronephrosis in infants and children.     

Clinical evaluation of renoscintigraphy using 123I-orthoiodohippurate--comparison with 131I-OIH and measurement of the effective renal blood flow

Renoscintigraphy using 123I-orthoiodohipprate (123I-OIH) was conducted, and the dynamic imaging study results and the renograms were analyzed. The results using 123I-OIH were compared with those using 131I-OIH in 22 of 33 patients. Measurement of the effective renal blood flow (ERBF) was also performed using 123I-OIH by the single blood-sample method. 123I is a more suitable nuclide for gamma-camera scintigraphy than 131I in terms of physical characteristics, and a larger dose of 123I-OIH is possible than 131I-OIH because of its lesser radiation. These are the reasons why clearer dynamic images of the blood flow phase, functional phase and excretion phase can be obtained. These make possible diagnoses associated with the organic changes and functions. No essential differences could be found in the functional study results of renogram between the two drugs because on the nuclide of 131I is replaced by 123I, but a renogram with less statistical noise could be obtained using 123I-OIH than 131I-OIH. The radiation dose of 123I-OIH is less than that of 131I-OHI, and clearer dynamic images and functional indexes can be easily obtained in scintigraphy using 123I-OIH. It is concluded that 123I-OIH is a useful radiopharmaceutical for renal examination, and it should replace 131I-OIH.     

The engymetric determination of acute functional impairment in kidney graft function caused by cyclosporine A

Engymetry offers a new means of continuously measuring nuclear radiation fields without any need of restricting the patient's mobility. In this study, kidney function was measured simultaneously and continuously for 6.6 h with engymetry, after application of a 12 h therapy dose of Cyclosporine A (CsA) of 4.0 +/- 1.8 mg per kg bodyweight (bw). 15 kidney transplanted patients participated in this study. 370 MBq 99Tcm-DTPA and 10 MBq 131I-OIH were injected during routine transplant scintigraphy. Renal function was monitored from the external disappearance curves of the tracers recorded by portable double radionuclide detectors. Renal impairment could be seen in the rising phase of CsA or coincided with the CsA maximum in 13 of the 15 patients. Under the impairment the half-life of 99Tcm-DTPA increased from 4.1 +/- 1.2 to 15.9 +/- 12.3 h (p less than 0.005) for 61 +/- 45 min and the half-life of 131I-OIH increased from 3.2 +/- 0.7 to 12.7 +/- 8.4 h (p less than 0.001) for 71 +/- 37 min. With noninvasive engymetry it is possible to detect renal functional impairment during long observation periods. Acute restriction in glomerular filtration and renal blood flow was discovered in human kidney graft recipients after the application of a low therapeutic CsA dose.     

123I-hippuran renal scintigraphy with evaluation of single-kidney clearance for predicting renal scarring after acute urinary tract infection: comparison with (99m)Tc-DMSA scanning.

The value of (123)I-hippuran (OIH) renal sequential scintigraphy (RSS) in predicting the evolution of defects detected by (99m)Tc-dimercaptosuccinic acid (DMSA) scanning during a first episode of acute pyelonephritis (APN) was assessed. METHODS: Fifty-eight children with APN underwent (99m)Tc-DMSA planar scanning and (123)I-OIH RSS during acute infection and at least 5 mo later. Renal lesions found by (99m)Tc-DMSA scanning were classified according to the following (99m)Tc-DMSA grading system: 0 = normal, 1 = 1 lesion, 2 = 2 lesions, and 3 = diffuse damage with renal parenchymal subversion. Renal scarring was diagnosed whenever a renal cortical defect detected at the first (99m)Tc-DMSA examination persisted on the follow-up (99m)Tc-DMSA examination. Single-kidney clearance rate (Cl) was evaluated by a method that was previously validated at our institution and is based on time-activity curves measured on the heart and kidney areas by the region-of-interest technique. RESULTS: (99m)Tc-DMSA scanning showed renal damage in 76 kidneys and had negative findings for the remaining 40 kidneys (2 patients had bilaterally negative findings). (99m)Tc-DMSA scanning determined 40 kidneys to be grade 0, 49 to be grade 1, 21 to be grade 2, and 6 to be grade 3. For (99m)Tc-DMSA grades of 0-3, the corresponding Cl mean values (in mL/min/1.73 m(2) of body surface area [BSA]) were 292 +/- 33, 237 +/- 39, 210 +/- 54, and 140 +/- 53, respectively. The Spearman regression coefficient (R) demonstrated a significant correlation between (99m)Tc-DMSA grade and Cl (R = 0.69, P < 0.0001). Thirty-six of the lesions detected by staging (99m)Tc-DMSA were shown to have recovered on follow-up renal scans, whereas 40 developed scars. A significant difference in Cl was found between the 2 groups (P < 0.0002). The Cl cutoff value was determined by univariate discriminant analysis; a Cl value of 232 mL/min/1.73 m(2) of BSA discriminated best between scarred and nonscarred kidneys, with a specificity, sensitivity, positive predictive value, negative predictive value, and overall accuracy of 95%, 95%, 90%, 97%, and 95%, respectively. CONCLUSION: Cl evaluation, in the course of acute urinary tract infection, is highly valuable in predicting the fibrotic evolution of renal damage detected on acute (99m)Tc-DMSA scanning. Also, our data show close agreement between Cl and the grade determined by staging (99m)Tc-DMSA.     

Characteristic brain distribution of 1-(14)C-octanoate in a rat model of focal cerebral ischemia in comparison with those of (123)I-IMP and (123)I-iomazenil.

1-(11)C-Octanoate is a potential tracer for studying astroglial function in PET. To evaluate the usefulness of 1-(11)C-octanoate for studying ischemic stroke, we investigated the brain distribution of 1-(14)C-octanoate and compared it with N-isopropyl-p-(123)I-iodoamphetamine ((123)I-IMP) distribution (cerebral blood flow), (123)I-iomazenil ((123)I-IMZ) distribution (neuronal viability based on (123)I-IMZ binding to benzodiazepine receptors), and hematoxylin-eosin stain (morphologic changes) in a rat model of focal cerebral ischemia. METHODS: The right middle cerebral artery of each rat was occluded intraluminally. The brain distribution of 1-(14)C-octanoate and (123)I-IMP (or (123)I-IMZ) was determined 4 and 24 h after the insult using a dual-tracer autoradiographic technique (n = 4-7 in each group). Coronal brain sections adjacent to those used for autoradiography were stained with hematoxylin and eosin. Regions of interest (ROIs) were determined for 3 coronal slices, and asymmetry indices (AIs, lesion/normal hemisphere) of the tracer uptake were calculated. ROIs on the hemisphere with the lesion were classified into 4 groups: In region A, widespread necrotic cells were observed; in region B, necrotic cells were occasionally observed; in region C1, no morphologic changes were observed and the AIs for (123)I-IMP (or (123)I-IMZ) were 0.8. RESULTS: 1-(14)C-Octanoate uptake decreased in the regions where morphologic changes were observed (regions A and B) but was relatively preserved in the surrounding region without morphologic changes despite reduced (123)I-IMP and (123)I-IMZ uptake (region C1). In the region without morphologic changes (region C1), AIs for 1-(14)C-octanoate were significantly higher than those for (123)I-IMP (4 h, 0.73 +/- 0.23 for 1-(14)C-octanoate and 0.37 +/- 0.20 for (123)I-IMP, P < 0.0001; 24 h, 0.84 +/- 0.11 for 1-(14)C-octanoate and 0.44 +/- 0.15 for (123)I-IMP, P < 0.0001) and those for (123)I-IMZ (4 h, 0.83 +/- 0.19 for 1-(14)C-octanoate and 0.57 +/- 0.13 for (123)I-IMZ, P < 0.0001; 24 h, 0.91 +/- 0.13 for 1-(14)C-octanoate and 0.73 +/- 0.06 for (123)I-IMZ, P < 0.0001). CONCLUSION: 1-(14)C-Octanoate uptake was relatively preserved in the regions without morphologic changes despite reduced (123)I-IMP and (123)I-IMZ uptake. 1-(11)C-Octanoate may provide further functional information on the pathophysiology of ischemic stroke, reflecting astroglial function based on fatty acid metabolism.     

Acetazolamide assisted Tc-99m MAG3 renography to assess renal blood flow reserve

OBJECTIVE: The present study examines whether or not baseline and acetazolamide (ACZ) Tc-99m MAG3 renography can assess renal blood flow reserve. METHODS: Renography proceeded for 50 min after sequential injections of 370 MBq Tc-99m MAG3 for baseline renography and 10 min after a 1,000 mg injection of ACZ for ACZ renography. Effective renal plasma flow of renal cortex (cERPF) in each kidney and the percentage change in cERPF of those parameters (deltaERPF) were obtained before and after the administration of ACZ in 10 subjects without hypertension or diabetes (normal group), in 10 with essential hypertension (hypertensive group) and in 10 who had Type 2 diabetes with hypertension (diabetic group). A placebo test was performed in the 10 without hypertension or diabetes using distilled water instead of ACZ (placebo group). RESULTS: The placebo test performed in the 10 without hypertension or diabetes using distilled water instead of ACZ indicated that the parameter variance between the two types of renogram was below 3.2%. The cERPF of baseline and ACZ Tc-99m MAG3 renography and deltaERPF in the normal, hypertensive and diabetic groups were 89 +/- 10 and 110 +/- 10 ml/min, 89 +/- 14 and 117 +/- 22 ml/min, 100 +/- 23 and 112 +/- 23 ml/min, respectively, and 24.5 +/- 13.5%, 26.0 +/- 9.7% and 12.3 +/- 11.1%, respectively. The difference in the cERPF value was significant in the normal and hypertensive groups whereas this did not change in the diabetic group before or after ACZ administration. CONCLUSIONS: We suggested that the deltaERPF determined by baseline and ACZ Tc-99m MAG3 renography is a useful parameter for assessing renal blood flow reserve.     

Radiolabeling, biodistribution, and dosimetry of (123)I-mAb 14C5: a new mAb for radioimmunodetection of tumor growth and metastasis in vivo.

This study reports on the in vitro evaluation, biodistribution, and dosimetry of (123)I-labeled monoclonal antibody (mAb) 14C5, a new antibody-based agent proposed for radioimmunodetection of tumor growth and metastasis in vivo. METHODS: (123)I-mAb 14C5 was prepared by direct iodination and tested for stability in vitro. Binding assays were performed on human SK-BR-3 and HeLa carcinoma cells to investigate the antigen expression, antibody affinity, and kinetics of tracer binding. For the biodistribution and dosimetry study, 3- to 4-wk-old NMRI mice were injected intravenously with (123)I-mAb 14C5 (148.0 +/- 7.4 kBq per mouse) and killed at preset time intervals. Organs, blood, urine, and feces were counted for radioactivity uptake, and the data were expressed as the percentage injected dose per gram tissue (%ID/g tissue) or %ID. The MIRDOSE3.0 program was applied to extrapolate the estimated absorbed radiation doses for various organs to the human reference adult. RESULTS: (123)I-mAb 14C5 was obtained in radiochemical yields of 85.0% +/- 2.5% and radiochemical purities were >97%. The iodinated antibody demonstrated good in vitro stability with 93.6% +/- 0.1% of (123)I-mAb 14C5 remaining intact at 24 h after radiolabeling. (123)I-mAb 14C5 bound to SK-BR-3 cells (dissociation constant [K(d)] approximately 0.85 +/- 0.17 nmol/L) and HeLa cells (K(d) approximately 1.71 +/- 0.17 nmol/L) with nanomolar affinity and high specificity, whereas both cell types exhibited a high CA14C5 antigen expression (maximum number of binding sites [B(max)] = 40.6 +/- 5.2 and 57.1 +/- 9.6 pmol/L, respectively). In mice, (123)I-mAb 14C5 accumulated primarily in lungs (20.4 %ID/g), liver (15.1 %ID/g), and kidneys (11.1 %ID/g) within 5 min after injection. A delayed uptake was observed in stomach (12.8 %ID/g) and urinary bladder (8.7 %ID/g) at 3 and 6 h, respectively, after injection. Radioactivity clearance was predominantly urinary, with 44.9 +/- 4.5 %ID excreted during the initial 48 h after administration (cumulative amount). The highest absorbed radiation doses determined for the human reference adult were received by the urinary bladder wall (0.1200-0.1210 mGy/MBq), liver (0.0137-0.0274 mGy/MBq), uterus (0.0196-0.0207 mGy/MBq), and lower large intestine wall (0.0139-0.0258 mGy/MBq). The average effective dose resulting from a single (123)I-mAb 14C5 injection was estimated to be 0.017-0.022 mSv/MBq. CONCLUSION: (123)I-mAb 14C5 shows good in vitro biologic activity and favorable biodistribution properties for imaging carcinomas of different origin and provides an acceptable radiation dose to the patient.     

Kidney allografts and remaining contralateral donor kidneys before and after transplantation: assessment by quantitative (99m)Tc-DMSA SPECT.

We used (99m)Tc-dimercaptosuccinic acid (DMSA) quantitative SPECT (QDMSA) to assess the function of kidneys before harvesting and after transplantation as well as the function of remaining donor kidneys. METHODS: Nineteen kidney donors underwent a baseline QDMSA study before nephrectomy. The allografts of these kidneys were studied in recipients at 1 wk, 1-2 mo, and 6-15 mo after transplantation. The kidneys remaining in 16 donors were studied at 1-2 mo and 6-15 mo after harvesting. The parameters obtained in each SPECT study included functional volume, concentration of (99m)Tc-DMSA per cubic centimeter of renal tissue, and total kidney uptake. Clinical evaluation and determination of serum creatinine levels took place at the same time as SPECT. RESULTS: On the basis of the clinical evaluation, 14 grafts had normal function and 5 were impaired. The mean +/- SD of kidney uptake values expressed as percentage of baseline values were 131% +/- 30% in normal grafts versus 57% +/- 5% in impaired grafts at 1 wk (P < 0.01), 173% +/- 57% versus 65% +/- 10% at 1-2 mo (P < 0.001), and 190% +/- 50% versus 69% +/- 14% at 6-15 mo after transplantation (P < 0.01). Uptake values in the donors' remaining kidneys were 159% +/- 27% of baseline values at 1-2 mo and 164% +/- 30% at 6-15 mo after nephrectomy. Allografts and remaining kidneys showed a similar increase in total kidney uptake as a result of an increase in both functional volume and concentration. CONCLUSION: QDMSA may be a noninvasive assessment tool in kidney transplantation from living donors.     

Clinical study of nephrotoxicity following cis-diamminedichloroplatinum (II) (CDDP) combination chemotherapy assessed by 131I-OIH renogram

The renal function in 26 patients with malignant tumors (19 non-small cell lung cancers, 4 small cell lung cancers, 1 malignant lymphoma, 1 esophageal cancer, 1 malignant thymoma) who were treated with 43 times combination chemotherapy including CDDP was evaluated prospectively, by measuring of creatinine clearance (Ccr), fractional excretion of beta-2-microglobulin (FE beta 2MG), urinary N-acetyl-beta-glucosaminidase (NAG), and 131I-OIH or 123I-OIH renogram. The comparison of renogram and other parameters showed significant change in renogram (23/43, 53.5%), however other parameters such as Ccr, FE beta 2MG, NAG altered in only 10.3-34.9%. After the administration of CDDP, renograms were divided into distinctive 4 patterns as follows: 1) aggravation of obstructive pattern 2) early plateau pattern in excretory phase 3) intermittent pattern in excretory phase 4) prolongation of secretory phase. We consider these patterns suggest some obstructive change of urinary tract microscopically, that is proximal tubules damage due to cellular necrosis and tubular dilatation by CDDP. 131I-OIH or 123I-OIH renogram in delayed phase is useful for detection of renal dysfunction by CDDP administration.     

Biodistribution and dosimetry study of 123I-rh-annexin V in mice and humans

This study reports on the optimization of the labelling procedure of clinical grade 123I-rh-annexin V and on the investigation of the biodistribution and dosimetry of 123I-rh-annexin V, a tracer proposed for the study of apoptosis in mice and humans. Research grade 123I-rh-annexin V was prepared as described previously, whereas clinical grade 123I-rh-annexin V was prepared according to a modified IodoGen method. NMRI mice, 3-4 weeks of age, received research grade 123I-rh-annexin V (74.0+/-3.7 kBq/mouse) by intravenous (i.v.) injection and killed at preset time points. Afterwards, the collected organs, blood, urine and faeces were counted for radioactivity and determined as %ID/g tissue or %ID over time. Secondly, six volunteers with normal liver and kidney function underwent whole-body scans up to 21 h after i.v. injection of clinical grade 123I-rh-annexin V (345+/-38 MBq). Time-activity curves were generated for the organs of interest, e.g., thyroid, heart, liver, kidneys and whole body, by fitting the organ specific geometric mean counts, obtained from region of interest analysis of acquired images in humans. The MIRD formulation was applied to calculate the absorbed radiation doses for various organs. Clinical grade 123I-rh-annexin V was obtained in radiochemical yields of 87.0+/-6.5% and radiochemical purities >98%. In mice, research grade 123I-rh-annexin V accumulated primarily in liver, kidney, stomach and lung tissue, limiting its usefulness for imaging of ongoing apoptosis in the abdominal and thoracic region. Clearance was predominantly urinary. In humans, acquired images with the clinical grade radioligand showed low lung uptake, resulting in good imaging conditions for the thoracic region. On the other hand, delayed imaging of the abdominal region was impeded due to extensive bowel activity. The highest absorbed doses were received by the thyroid, the kidneys, the heart wall, the liver and bone surfaces. The average effective dose of 123I-rh-annexin V was estimated to be 0.02 mSv.MBq-1. The amount of 123I-rh-annexin V required for in vivo imaging, results in an acceptable effective dose to the patient.     

Is furosemide administration effective in improving the accuracy of determination of differential renal function by means of technetium-99m DMSA in patients with hydronephrosis

It has been suggested that determination of differential renal function (DRF)using technetium-99m dimercaptosuccinic acid (DMSA) may lead to overestimation of the function of an obstructed kidney in patients with excretion abnormalities owing to pelvic retention of DMSA. Recently published guidelines have recommended use of furosemide injection when calculating DRF in these particular patients. The aim of this study was to evaluate the effect of diuretic administration on the determination of DRF using DMSA scintigraphy. For this purpose, 19 patients, aged from 1 month to 69 years (19.4+/-24.8 years, 15 males, 4 females), in whom pelvic retention had been documented by diuresis scintigraphy were included in the study. DMSA scintigraphy was performed in all patients 2-4 h after injection and six planar images were obtained. Immediately after the standard study, furosemide was injected in all patients, and 30 min later the same number of images was obtained. DRF was calculated for each patient and from each DMSA study by using the arithmetic mean method. The difference between two studies (DMSA scintigraphy with or without furosemide administration and diuresis scintigraphy) was expressed as a percentage of the mean value of the two studies (the DRF value of the affected kidney was thus taken into account). The mean of the differences represented the systemic bias and the SD of the mean of the differences represented the precision of the technique. In seven patients, diuresis renography revealed an obstructive curve pattern. We did not observe any significant difference between the DRF values obtained before and after diuretic administration ( P>0.5). When we compared DRF values obtained from standard and from diuretic DMSA studies, the mean of the differences was only 0.3% and the SD was only 1.2%. There was also no significant difference in DRF between patients with the obstructive curve pattern and those with a dilated renogram curve pattern (with washout of activity during the second phase of the study) ( P>0.1). In conclusion, we did not observe interference from pelvicalyceal activity in patients with documented pelvic retention and infer that diuretic administration may be a useless intervention for improving the accuracy of determination of DRF.     

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.     

PET imaging of somatostatin receptors: design,synthesis and preclinical evaluation of a novel <Superscript>18</Superscript>F-labelled,carbohydrated analogue of octreotide

Because of the excellent nuclear properties of fluorine-18 and the growing interest in somatostatin receptor (sst) scintigraphy with PET, a novel carbohydrated (18)F-labelled sst ligand was developed and preclinically evaluated. Synthesis of N(alpha)-(1-deoxy- D-fructosyl)- N(epsilon)-(2-[(18)F]fluoropropionyl)-Lys(0)-Tyr(3)-octreotate ([(18)F]FP-Gluc-TOCA) was completed in approximately 3 h (20%-30% yield). [(19)F]FP-Gluc-TOCA showed no affinity to hsst1 and hsst3, moderate affinity to hsst4 (IC(50): 437+/-84 n M) and hsst5 (IC(50): 123+/-8.8 n M) and very high affinity to hsst2 (IC(50): 2.8+/-0.4 n M). As a result of carbohydration, lipophilicity of [(18)F]FP-Gluc-TOCA was found to be low (lg P(OW)=-1.70+/-0.02). In mice, the tracer was rapidly cleared via renal excretion (kidneys: 8.69%+/-1.09%ID/g) and showed low uptake in liver (0.72%+/-0.14%ID/g) and intestine (1.88%+/-0.52%ID/g) and high tumour uptake (13.54%+/-1.47%ID/g) (all data at 1 h p.i.). Tumour to non-tumour ratios at 60 min p.i. reached 25, 19, 7, 1.6 and 56 for blood, liver, intestine, kidney and muscle, respectively. A similar biodistribution pattern was observed in pancreatic tumour-bearing rats. Tumour uptake in rats was reduced to 36% and 18% of control (30 and 60 min) by co-injection of 500 microg Tyr(3)-octreotide, demonstrating sst-specific uptake. In a first [(18)F]FP-Gluc-TOCA-PET study of a patient with a metastatic carcinoid in the liver the tracer showed superior pharmacokinetics, e.g. rapid urinary excretion and low uptake in liver, kidney and spleen. Multiple liver lesions (SUVs ranging from 21.4 to 38.0) and previously unknown focal uptake in the abdomen (SUV 10.0) were clearly visible. This is the first report on PET imaging using an (18)F-labelled sst binding peptide; it indicates that [(18)F]FP-Gluc-TOCA offers excellent imaging characteristics and allows sst imaging with high tumour to non-tumour contrast.     

Diagnostic performance of an expert system for interpretation of 99mTc MAG3 scans in suspected renal obstruction.

The purpose of the study was to compare diuresis renography scan interpretation generated by a renal expert system with the consensus interpretation of 3 expert readers. METHODS: The expert system was evaluated in 95 randomly selected furosemide-augmented patient studies (185 kidneys) obtained for suspected obstruction; there were 55 males and 40 females with a mean age +/- SD of 58.6 +/- 16.5 y. Each subject had a baseline (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3) scan followed by furosemide administration and a separate 20-min acquisition. Quantitative parameters were automatically extracted from baseline and furosemide acquisitions and forwarded to the expert system for analysis. Three experts, unaware of clinical information, independently graded each kidney as obstructed/probably obstructed, equivocal, and probably nonobstructed/nonobstructed; experts resolved differences by a consensus reading. These 3 expert categories were compared with the obstructed, equivocal, and nonobstructed interpretations provided by the expert system. Agreement was assessed using weighted kappa, and the predictive accuracy of the expert system compared with expert readers was assessed by the area under receiver-operating-characteristic (ROC curve) curves. RESULTS: The expert system agreed with the consensus reading in 84% (101/120) of nonobstructed kidneys, in 92% (33/36) of obstructed kidneys, and in 45% (13/29) of equivocal kidneys. The weighted kappa between the expert system and the consensus reading was 0.72 and was comparable with the weighted kappa between experts. There was no significant difference in the areas under the ROC curves when the expert system was compared with each expert using the other 2 experts as the gold standard. CONCLUSION: The renal expert system showed good agreement with the expert interpretation and could be a useful educational and decision support tool to assist physicians in the diagnosis of renal obstruction. To better mirror the clinical setting, algorithms to incorporate clinical data must be designed, implemented, and tested.