Diethylenetriaminepentaacetic Acid-galactosyl Human Serum Albumin Research Articles

Usefulness of Liver Uptake Rate Constant in 99mTc-GSA Scintigraphy for the Risk Stratification of Patients Undergoing Hepatectomy: A New Method for Calculation

Introduction: The use of technetium 99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin (^99mTc-GSA) scintigraphy parameters, HH15 and LHL15, in assessing the future liver remnant function is not expedient because of their nonlinear behaviour against liver volume. Uptake rate constant for the binding of ^99mTc-GSA to asialoglycoprotein receptors is probably more favourable, but the reported calculation methods are complex. We devised a simple method to calculate the uptake rate constant, KrGSA. Methods: Radioactivity counts for the entire liver and heart regions were extracted at 10, 20, and 30 min. Using whole liver and heart volumes measured from single-photon emission computed tomography images, free radioactivity corresponding to the liver blood pool was subtracted. The time activity curve was fitted to the equation L(t) = L(∞) × [1 − Exp (−kt)] using Microsoft Office Excel (add-in free programme Solver)®, where L(∞) is the count at plateau level and k denotes KrGSA. Results: KrGSA values accurately identified liver cirrhosis and were similar to the KICG. The areas under the curve for KrGSA and KICG in the receiver operating characteristic analysis were 0.808 and 0.795, respectively, and a good correlation was seen between KrGSA and KICG. Discussion/Conclusion: KrGSA can be utilized as an alternative to KICG in assessing the future liver remnant function.

99mTc-GSA scintigraphy for assessing the functional volume ratio of the future liver remnant in the routine practice of liver resection

BackgroundThe significance of incorporating regional functional heterogeneity assessment by liver scintigraphy into the calculation of the future liver remnant has been reported. However, liver scintigraphy entails additional costs and radiation exposure. Nevertheless, studies describing when liver scintigraphy demonstrates an actual benefit over computed tomography liver volumetry are lacking. Thus, we evaluated the degree of agreement between future liver remnant % values calculated by technetium 99mTc diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy (galactosyl human serum albumin–based future liver remnant %) and those by computed tomography volumetry and investigated the practical impact of performing regional functional heterogeneity assessment. MethodsThe Bland–Altman method was used to retrospectively analyze the agreement between computed tomography– and galactosyl human serum albumin–based future liver remnant % measurements in 84 patients. ResultsIn ordinary patients with a computed tomography–based future liver remnant % greater than 50%, there was a good agreement between both measurements. However, in cases with a computed tomography–based future liver remnant % less than 40%, galactosyl human serum albumin–based measurements were significantly smaller than computed tomography–based values, with 88% of these patients exhibiting a galactosyl human serum albumin–based future liver remnant % less than 30%. After portal vein embolization, galactosyl human serum albumin–based measurements were primarily greater than or in agreement with computed tomography–based values, even in cases with a computed tomography–based future liver remnant % less than 40%. ConclusionAdding 99mTc diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy to computed tomography liver volumetry is advised when deciding on hepatectomy in patients with a computed tomography–based future liver remnant % less than 50%. If the computed tomography–based future liver remnant % is smaller than 40%, it is strongly recommended to check future liver remnant % by 99mTc diethylenetriaminepentaacetic acid-galactosyl human serum albumin scintigraphy. In other cases, computed tomography–based future liver remnant % calculation alone can be regarded as the gold standard of safe hepatectomy.

Fractal Dimension of Tc-99m DTPA GSA Estimates Pathologic Liver Injury due to Chemotherapy in Liver Cancer Patients.

Chemotherapy-induced liver injury after potent chemotherapy is a considerable problem in patients undergoing liver resection. The aim of this study was to assess the relationship between the fractal dimension (FD) of Tc-99m diethylenetriaminepentaacetic acid (DTPA) galactosyl human serum albumin (GSA) and pathologic change of liver parenchyma in liver cancer patients who have undergone chemotherapy. We examined 34 patients (10 female and 24 male; mean age, 68.5 years) who underwent hepatectomy. Hepatic injury was defined as steatosis more than 30%, grade 2-3 sinusoidal dilation, and/or steatohepatitis Kleiner score ≥4. Fractal analysis was applied to all images of Tc-99m DTPA GSA using a plug-in tool on ImageJ software (NIH, Bethesda, MD). A differential box-counting method was applied, and FD was calculated as a heterogeneity parameter. Correlations between FD and clinicopathological variables were examined. FD values of patients with steatosis and steatohepatitis were significantly higher than those without (P>.001 and P>.001, respectively). There was no difference between the FD values of patients with and without sinusoidal dilatation (P=.357). Multivariate logistic regression showed FD as the only significant predictor for steatosis (P=.005; OR 36.5; 95% CI 3.0-446.3) and steatohepatitis (P=.012; OR, 29.1; 95% CI 2.1-400.1). FD of Tc-99m DTPA GSA was the significant predictor for fatty liver disease in patients who underwent chemotherapy. This new modality is able to differentiate steatohepatitis from steatosis; therefore, it may be useful for predicting chemotherapy-induced pathologic liver injury.

Functional discrepancy between two liver lobes after hemilobe biliary drainage in patients with jaundice and bile duct cancer: an appraisal using (99m)Tc-GSA SPECT/CT fusion imaging.

To determine the functional discrepancy between the two liver lobes using technetium 99m ((99m)Tc) diethylenetriamine-pentaacetic acid-galactosyl human serum albumin ( GSA diethylenetriamine-pentaacetic acid-galactosyl human serum albumin ) single photon emission computed tomography (SPECT)/computed tomography (CT) fusion imaging following preoperative biliary drainage and portal vein embolization ( PVE portal vein embolization ) in patients with jaundice who have bile duct cancer ( BDC bile duct cancer ). This retrospective study was approved by the institutional review board, with waiver of informed consent. Preoperative (99m)Tc- GSA diethylenetriamine-pentaacetic acid-galactosyl human serum albumin SPECT/CT fusion images from 32 patients with extrahepatic BDC bile duct cancer were retrospectively reviewed. Patients were classified into four groups according to the extent of biliary drainage and presence of a preoperative right PVE portal vein embolization : right lobe drainage group (right drainage), bilateral lobe drainage group (bilateral drainage), left lobe drainage group (left drainage), and left lobe drainage with right PVE portal vein embolization group (left drainage with right PVE portal vein embolization ). Percentage volume and percentage function were measured in each lobe using fusion imaging. The ratio between percentage function and percentage volume (the function-to-volume ratio) was calculated for each lobe, and the results were compared among the four groups. Statistical analysis was performed with Wilcoxon signed-rank tests and Mann-Whitney U tests. The median values for the function-to-volume ratio in the right drainage, bilateral drainage, left drainage, and left drainage with right PVE portal vein embolization group were 1.12, 1.05, 1.02, and 0.81 in the right lobe; and 0.51, 0.88, 0.96, and 1.17 in the left lobe. Significant differences in the function-to-volume ratio were observed among the four groups (right drainage vs bilateral drainage vs left drainage vs left drainage with right PVE portal vein embolization ; with P < .002, P = .023, and P < .002 for the right lobe and P < .001, P = .023, and P < .002 for the left lobe). Hepatic lobar function significantly differs between the two lobes, depending on the extent of biliary drainage and the presence of portal vein embolization.

A novel liver function evaluation system using radiopharmacokinetic modeling of technetium-99m-DTPA-galactosyl human serum albumin

A new kinetic model of technetium-99m-labeled diethylenetriaminepentaacetic acid-galactosyl human serum albumin (Tc-GSA) was developed to show the speed of asialoglycoprotein receptor-mediated endocytosis. Ten healthy volunteers and 17 patients with liver cirrhosis were intravenously injected with 185 MBq of Tc-GSA, and dynamic planar images were acquired. The absolute amounts of Tc-GSA in the liver and extrahepatic blood were estimated from the time-activity curves for the liver, heart, and lungs. A two-compartment model was represented with two parameters as variables to estimate the uptake index (UI) of Tc-GSA transport through the hepatic cell membrane from the total plasma at any given time. The dynamic curve of Tc-GSA uptake by the liver was generated. Analysis of individuals with normal livers and patients with liver cirrhosis showed statistically significant differences in their UI. The UI for normal livers was high and that for cirrhotic livers was low. Linear regression correlation of UI with albumin, prealbumin, and prothrombin time was 0.841, 0.746, and -0.723, respectively. UI reflects the cellular transport of asialoglycoproteins as ascertained by the two-compartment model on the basis of GSA dynamic images. It is useful for measuring liver function.

Recurrent Hepatitis C After Living Donor Liver Transplantation Detected by Tc-99m GSA Liver Scintigraphy

Recurrence of hepatitis C virus (HCV) after living donor liver transplantation was investigated using technetium-99m- diethylenetriaminepentaacetic acid-galactosyl human serum albumin (Tc-99m-GSA) liver scintigraphy. Four patients with decompensated cirrhosis due to HCV infection were retrospectively reviewed in this study. Scintigraphy was performed to determine the hepatic uptake ratio of the tracer corrected for disappearance from the blood, as well as the maximal removal rate of the tracer by hepatocytes, as parameters of hepatic functional reserve. In all patients, serum HCV ribonucleic acid (RNA) was detected 3 months after transplantation. The corrected hepatic uptake ratio and removal rate showed little change after transplantation in two patients without the recurrence of HCV infection. In another two patients, these levels were decreased at 3 months after transplantation. In one patient, recurrent HCV infection was diagnosed by confirmatory histologic examination at 12 months after transplantation. In the other patient, both levels declined further at 8 months. Although treatment was initiated with a combination of interferon plus ribavirin, this patient died of progressive hepatic failure. In conclusion, a decrease in scintigraphic parameters at 3 months after transplantation suggests recurrent HCV infection affecting the graft. Tc-99m-GSA liver scintigraphy is a useful noninvasive method for evaluating graft functional reserve.

Binding rate constant of Tc-99m DTPA galactosyl human serum albumin measured by quantitative dynamic SPECT--clinical evaluation as a total and regional liver function test.

To evaluate the clinical utility of a new method with dynamic single photon emission computed tomography (SPECT) and scatter and attenuation compensation to estimate both total and regional liver function quantitatively. Five controls, 20 patients with chronic liver disease, and 2 patients with Budd-Chiari syndrome were studied. Dynamic liver SPECT data were acquired during 20 minutes after injection of Technetium (Tc)-99m diethylenetriaminepentaacetic acid (DTPA) galactosyl human serum albumin (GSA) with scatter and attenuation compensation. The binding rate constant of Tc-99m GSA (Ku) was derived quantitatively from the Patlak plot based on kinetic models for GSA receptor binding. The mean Ku was obtained by dividing the Ku value (total Ku) by the liver volume. Both total and mean Ku were significantly lower in patients with chronic liver disease than in controls (302 +/- 112 vs. 523 +/- 78 ml/min; p < 0.001, 0.26 +/- 0.11 vs. 0.43 +/- 0.03 ml/min/cm3; p < 0.001). In the patient group, both total and mean Ku were significantly correlated with the results of conventional liver function tests and the histological severity of chronic liver disease. In 2 patients with Budd-Chiari syndrome, the mean Ku was lower in the right lobe, where the hepatic veins were occluded, than in the left lobe, where draining veins were patent. In conclusion, this method is a reliable diagnostic technique for estimating total and regional liver function.

Usefulness of Technetium‐99m‐Galactosyl Human Serum Albumin Liver Scintigraphy for Assessment of Severity of Alcoholic Hepatitis

We performed a liver scintigraphy using technetium-99m diethylene-triaminepentaacetic acid-galactosyl human serum albumin (99mTc-GSA), which images the functional liver mass through its binding to the specific receptor asialoglycoprotein receptor in patients with severe alcoholic hepatitis. Receptor index (LHL 15) was significantly lower in patients with alcoholic hepatitis, compared with controls with normal liver. Difference in the isotope uptake patterns between liver and heart varied according to the severity of liver disease, and made it possible to categorize 5 grades. Grading score could discriminate between the eventual outcome of the patients. Furthermore, single photon emission computed tomography showed the variable uptake patterns in the hepatic lobule, wherein there were no evident findings in macroscopic view at autopsy. The results of this study show the usefulness of 99mTc-GSA scintigraphy in the evaluation and prognosis of alcoholic hepatitis.

Functional liver imaging with asialoglycoprotein receptors and serum hyaluronate in a patient with amyloidosis

A 47-year-old man with primary amyloidosis was admitted with abdominal pain. A new radionuclide liver imaging technique using Technetium-99m diethylenetriamine-pentaacetic acid-galactosyl human serum albumin, was performed and the serum hyaluronate concentration was measured. Although ordinary laboratory tests revealed only slight abnormalities, the uptake of the radiolabelled ligand for hepatocyte asialo-glycoprotein receptors was decreased, and marked hepatomegaly was revealed. Furthermore, the serum hyaluronate level was elevated. Histological examination of a hepatic needle biopsy specimen revealed a marked deposition of amyloid in the hepatic perisinusoidal spaces. These results indicate that this new radionuclide liver imaging technique (using Technetium-99m diethylenetriamine-pentaacetic acid-galactosyl human serum albumin) and the measurement of serum hyaluronate may be useful supplementary tools for identifying amyloid deposition in the hepatic perisinusoidal spaces in patients with amyloidosis.

Asialoglycoprotein receptor function of hepatocytes in patients with autoimmune hepatitis.

To assess whether the hepatocyte asialoglycoprotein receptors are affected in patients with autoimmune hepatitis, the function of the hepatocyte asialoglycoprotein receptor was investigated in patients with autoimmune hepatitis or chronic hepatitis C. A new radionuclide liver imaging technique, Technetium-99m diethylenetriamine-pentaacetic acid-galactosyl human serum albumin, was applied to evaluate the function of the receptor. A Receptor Index (LHL 15) was calculated by dividing the radioactivity of the liver region-of-interest (ROI) by that of the liver plus heart ROI 15 min after radiolabeled ligand injection. Serum albumin, prothrombin time, hepaplastin test and plasma retention rate of indocyanine green at 15 min were not significantly different between patients in the autoimmune hepatitis group and chronic hepatitis C group. In addition, the Receptor Index of patients with autoimmune hepatitis, in whom the asialoglycoprotein receptor is a candidate target antigen for autoimmune response, was similar to that of patients with chronic hepatitis C. These results indicate that the hepatocyte receptor for asialoglycoproteins is not affected in patients with autoimmune hepatitis.

Function of Asialoglycoprotein Receptor of Hepatocytes in Patients with Wilson's Disease.

The function of hepatocyte asialoglycoprotein receptors was analyzed in normal subjects, in patients with Wilson's disease and in patients with chronic hepatitis C. A new radionuclide liver imaging, using Technetium-99m diethylenetriamine-pentaacetic acid-galactosyl human serum albumin, was applied to evaluate the function of the receptor, and a Receptor Index, LHL 15, which was calculated by dividing the radioactivity of the liver region-of-interest (ROI) by that of the liver plus heart ROI at 15 min after the radiolabeled ligand injection, was evaluated. The values were similar between the patients with Wilson's disease and patients with chronic hepatitis C. Hepatocyte receptors for asialoglycoproteins were not affected specifically in patients with Wilson's disease, suggesting that the defect in patients with Wilson's disease involves steps other than receptor-mediated endocytosis of asialoceruloplasmin via asialoglycoprotein receptor.

Quantitative assessment of hepatocellular function through in vivo radioreceptor imaging with technetium 99m galactosyl human serum albumin

Technetium 99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin is a newly developed analog ligand to asialoglycoprotein receptor, which is a hepatic cell surface receptor specific for galactose-terminated glycoproteins. Hepatic functional imaging, which yields estimates of asialoglycoprotein receptor concentration, was performed after intravenous injection of 3 mg technetium 99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin. A total of 75 human subjects were studied: 6 controls without liver diseases, 51 patients with chronic liver diseases and 18 patients with acute liver diseases. In chronic liver disease the asialoglycoprotein receptor concentration significantly correlated with the clinical severity based on the criteria of the Liver Cancer Study Group of Japan (rs = -0.890, p = 0.0001). Good correlations between the asialoglycoprotein receptor concentration and conventional liver function tests were also observed. In acute liver disease the asialoglycoprotein receptor concentration correlated well with the normotest (r = 0.796, p = 0.0001), prothrombin time (r = 0.701, p = 0.0002) and total serum bilirubin (r = -0.642, p = 0.0007). We conclude that the parameter, asialoglycoprotein receptor concentration, obtained from the kinetic analysis of technetium 99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin time-activity data, is a sensitive measure of functioning hepatocyte mass in acute and chronic liver disease.

Functional hepatic imaging with receptor-binding radiopharmaceutical: clinical potential as a measure of functioning hepatocyte mass.

Asialoglycoprotein receptor (ASGP-R) is a hepatic cell surface receptor specific for galactose-terminated glycoproteins. Technetium-99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin (TcGSA) is a newly developed analog ligand to ASGP-R. Fourteen human subjects were studied: three normal volunteers, one with chronic hepatitis, 6 with liver cirrhosis, and 4 with hepatocellular carcinoma associated with liver cirrhosis. The receptor index parameter (LHL15), was obtained from the liver and heart time-activity data as the ratio of radioactivity of the liver over that of the liver plus heart at 15 min after intravenous injection of 1 mg of TcGSA. Means +/- standard deviations of LHL15 in normal volunteers (3 cases), patients with mild (4 cases), moderate (2 cases), and severe liver damage (5 cases) were 0.933 +/- 0.006, 0.789 +/- 0.045, 0.723 +/- 0.033, and 0.488 +/- 0.094, respectively. The difference between the mean values of each group was statistically significant (P less than 0.05). LHL15 correlated well with classical indicators for hepatic functional capacity such as serum albumin level, serum bilirubin level, prothrombin time, ICG R15 or Child-Turcotte criteria score. Our preliminary experiences of high correlations of TcGSA functional imaging data with clinical data suggest that the dynamic data using this receptor-binding radiopharmaceutical provides invaluable information with regard to liver function, and thus, the TcGSA study is potentially a noninvasive practical tool to measure functioning hepatocyte mass.