Ligandin binding phthalein complexone complex of technetium for hepatic function studies

In our pursuit for liver functional diagnosis, development of bifunctional radiopharmaceutical containing iminodiacetic acid (IDA), as the technetium chelating site along with phthalein or fluorescein structure, the skeleton of BSP and Rose Bengal, long used for the assessment of liver function is considered. Among the various PC, PPC, TPC and calcein IDA derivatives commercially available,^99mTc-PC (PC: 3,3-bis(N, N-dicarboxymethylaminomethyl)o-cresolphthalein) showed the highest hepatobiliary excretion. The functionality of the various technetium labeled phthalein and fluorescein IDA derivatives was evaluated by competitive BSP binding studies and by comparative binding with the hepatocyte specific protein, ligandin.     

Ligandin binding phthalein complexone complex of technetium for hepatic function studies

In our pursuit for liver functional diagnosis, development of bifunctional radiopharmaceutical containing iminodiacetic acid (IDA), as the technetium chelating site along with phthalein or fluorescein structure, the skeleton of BSP and Rose Bengal, long used for the assessment of liver function is considered. Among the various PC, PPC, TPC and calcein IDA derivatives commercially available, 99mTc-PC (PC: 3,3'-bis(N, N-dicarboxymethylaminomethyl)o-cresolphthalein) showed the highest hepatobiliary excretion. The functionality of the various technetium labeled phthalein and fluorescein IDA derivatives was evaluated by competitive BSP binding studies and by comparative binding with the hepatocyte specific protein, ligandin.     

Evaluation of six new 99mTc-IDA agents for hepatobiliary imaging

IDA derivatives of three substituted benzothiazol, and two substituted chlorophenyl and one substituted pyrazoline compounds have been labeled with 99mTc and screened with four rat models with hepatocellular dysfunction manifesting varying degrees of change of liver architecture and hepatocellular damage associated with an active parenchymal destruction, fatty metamorphosis and cirrhosis. Organ distribution studies at 1 h postinjection have been compared in normal and diseased animal models for each agent labeled with 99mTc and with 99mTc-Disofenin (Disida) and Lidofenin (Hida) and 131I-Rose Bengal. From the data obtained with the six new IDA derivatives, the distribution kinetics of 99mTc-Arclophenin, (N-N'-2-benzoyl-4-chlorophenyl)carbamoylmethyl) imino diacetic acid (Phenida), are closely comparable to 99mTc-Disofenin in all animal models. Crossover patient studies (n = 14) for clinical evaluation of 99mTc-Arclophenin vs 99mTc-Disofenin indicate the close similarity of the 2 agents with regard to blood pool retention, gross liver/heart ratios and liver washout, suggesting Arclofenin as a suitable agent for hepatobiliary function studies. The impaired hepatocellular animal models presented should serve for fast screening of hepatobiliary agents and enable comparison of a series of closely related compounds.     

A quantitative method for estimating hepatic blood flow using a dual-input single-compartment model

The purpose of this study was to investigate the accuracy of a quantitative method for estimating arterial hepatic blood flow and portal hepatic blood flow separately using a dual-input single-compartment model compared with the maximum slope method using computer simulations and clinical data. In computer simulations, the rate constants for the transfer of contrast agent (CA) from the hepatic artery to the liver (K(1a)), from the portal vein to the liver (K(1p)) and from the liver to the blood (k(2)) were estimated from simulated time-density curves with various transit times of CA from the aorta to the liver (tau(a)) and from the portal vein to the liver (tau(p)) using the linear least-squares (LLSQ) method. In clinical studies, dynamic CT data were acquired from 27 patients, and parametric maps of K(1a), K(1p) and k(2) were generated by applying the LLSQ method pixel by pixel. In simulation studies, tau(a) and tau(p) were found to have a large and a small effect on the estimates of K(1a) and K(1p), respectively. In clinical studies, the K(1a) and K(1p) values estimated with the maximum slope method were underestimated by 60+/-29% and 37+/-12%, respectively, compared with those estimated by the LLSQ method. In conclusion, our results suggest that correction of tau(a) is necessary for accurately estimating K(1a) and K(1p). Our method is therefore promising for the evaluation of hepatic blood flow in various liver diseases because it allows us to evaluate arterial hepatic blood flow and portal hepatic blood flow separately and visually.     

Scintigraphic findings mimicking focal nodular hyperplasia in a case of hepatoblastoma.

Hepatoblastoma is a primary liver neoplasm in which prompt diagnosis and resection are critical to long-term survival. Liver scintigraphy using Tc-99m sulfur colloid and Tc-99m iminodiacetic acid (IDA) derivatives has been used in the evaluation of hepatic masses. Most space-occupying lesions of the liver appear as photopenic regions following either Tc-99m SC or IDA agents. Two exceptions have been reported. Focal nodular hyperplasia (FNH) has been shown to have variable colloid uptake, which is dependent upon the number of Kupffer cells per given volume. Many patients with FNH will demonstrate activity within the FNH to be greater or equal to the normal liver. In addition, two cases of hepatoblastoma have been reported to show colloid activity within the tumor, and in one patient slight uptake of Tc-99m IDA was noted in the tumor 15 minutes postinjection. The current case demonstrates a hepatoblastoma in which the scintigraphic findings with Tc-99m SC and Tc-99m IDA were similar to those reported, with retention of IDA far greater than the previously reported case.     

Indium-111 labeled leukocyte imaging following hepatic artery embolization

The use of In-111 labeled leukocytes for abscess localization is becoming well established. The first report of In-111 imaging following hepatic embolization is presented. A 45-year-old man with adenocarcinoma of the colon and metastatic liver disease was treated for intractable pain using particulate embolization of the hepatic artery. In-111 leukocyte imaging was performed to rule out abscess formation. The distribution of the labeled leukocytes demonstrated hepatic uptake commensurate with Tc-99m sulfur colloid (SC) images. Areas of embolization did not accumulate tracer. Pathologic examination at autopsy correlated with the distribution of the labeled leukocytes. Thus, therapeutic embolization did not alter the normal distribution of this tracer in functional hepatic tissue.     

Radionuclide evaluation of liver transplants

Orthotopic liver transplantation is now an established technique for treating patients with various forms of end stage liver disease. The number of centers performing the procedure is increasing and, as the number of transplant recipients in the population increases, many institutions performing nuclear medicine studies will be confronted with requests to evaluate these patients. While a variety of radionuclides are proving useful in this evaluation, the 99mTc iminodiacetic acid (IDA) compounds, particularly 99mTc diisopropyl IDA (DISIDA), will probably account for the majority of radionuclide evaluations of these patients because they are well suited to monitor both structural and functional changes of the graft. The primary application of radionuclide studies is focused in the postoperative period, when problems with the vascular and biliary anastomoses, rejection, infections, and bile leaks all produce alterations in radionuclide hepatobiliary studies. Abnormalities such as rejection and infection produce primarily functional, rather than structural changes and are not easily differentiated based upon the kinetics of 99mTc-DISIDA extraction and excretion by the liver, serial imaging and correlation with clinical data is necessary in such situations. Quantitative analyses of kinetic 99mTc IDA (DISIDA) studies and quantitative approaches with other compounds such as 99mTc galactosyl-neoglycoalbumin (NGA) may permit better assessments of relatively subtle changes in liver function in the posttransplant period.     

Indium-111 platelet kinetics in patients with diabetes mellitus

We performed in vitro aggregation and indium-111 labeled platelet kinetic and biodistribution studies in seven patients with diabetes mellitus and in five control subjects. All subjects were male. All diabetic patients were poorly controlled at the time of study with blood glucose greater than 140 mg % and hemoglobin A1c greater than 10%. In vivo kinetic and biodistribution studies were performed following reinjection of autologous platelets labeled with indium-111 oxine in a dose of approximately 50 microCi (42-67 microCi). Images obtained at 4 and 24 h were computer-analyzed to determine splenic and hepatic uptake, and platelet survival times were calculated using four mathematical models. Unexpectedly, diabetic patients with fewer vascular complications tended to have shorter platelet survival times than patients with advanced vascular disease. However, no significant differences were observed between diabetic and control groups for any of the parameters of platelet function evaluated.     

Diagnosis of liver cirrhosis by transit-time analysis at contrast-enhanced ultrasonography

Purpose

The aims of this prospective study were to evaluate analysis of sulfur-hexafluoride-filled microbubble contrast agent (Sonovue) transit times as a tool for differentiating liver cirrhosis from the noncirrhotic stage of liver disease and to compare its performance with that of conventional B-mode and Doppler ultrasonography (US).

Materials and methods

Contrast-enhanced hepatic ultrasonography with the US contrast agent Sonovue was performed on 38 patients with diagnoses of hepatic cirrhosis based on unequivocal clinical signs or liver biopsy findings (Child-Pugh classes A in 19, B in 16 and C in three), 31 patients with noncirrhotic diffuse liver disease (biopsy confirmed) and 14 controls without diffuse liver disease. Time curves of hepatic-vein signal intensity were analysed using objective criteria to determine the time of enhancement onset (hepatic-vein arrival time) and peak enhancement (hepatic-vein peak enhancement). Accuracy in diagnosing cirrhosis was compared with that based on B-mode and Doppler data.

Results

Hepatic-vein arrival time in cirrhotic patients was significantly shorter (p<0.01) than in noncirrhotic (chronic liver disease and controls) patients. Peak enhancement times in these three groups were not significantly different. An arrival-time cutoff of 17 s distinguished cirrhotic from noncirrhotic patients with high accuracy (100% sensitivity, 93.3% specificity, positive and negative predictive values 92.6% and 100%, respectively) and excellent reproducibility (kappa coefficients of 1.0 and 0.93 for intraand interobserver agreement). Contrast-enhanced US showed better sensitivity than the B-mode and Doppler data.

Conclusions

Analysis of the time of onset of US contrast enhancement of the hepatic vein appears to be a potentially useful noninvasive supplement to conventional sonography and Doppler in the follow-up of patients with chronic diffuse liver disease.     

Preliminary findings in the evaluation of hepatic malignancies by radioimmunodetection, X-ray computed tomography, and magnetic resonance imaging

In 12 consecutive patients with suspected metastatic carcinoma of the liver, we evaluated the sensitivity of radiolabeled antibodies to tumor antigens, magnetic resonance imaging, and X-ray computed tomography imaging in the detection of hepatic malignancies. Studies were performed with 131I labeled antibodies to CEA and/or CSAp; polyclonal, monoclonal and F(ab')2 antibodies were used. Nontarget radioactivity was diminished by administration of 99mTc reagents simulating nontumor distribution and use of a computer subtraction method. In nine patients with confirmed liver neoplasms, radioimmunodetection disclosed the foci of hepatic malignancies. In three patients with suspected liver neoplasms, the antibody studies were positive, but at this time have not been confirmed. X-ray computed tomography each disclosed mass lesions in five patients and magnetic resonance in three. These findings suggest that radioimmunodetection provides greater accuracy in the detection and localization of cancer than other diagnostic modalities currently used.     

Preliminary findings in the evaluation of hepatic malignancies by radioimmunodetection,X-ray computed tomography,and magnetic resonance imaging

In 12 consecutive patients with suspected metastatic carcinoma of the liver, we evaluated the sensitivity of radiolabeled antibodies to tumor antigens, magnetic resonance imaging, and X-ray computed tomography imaging in the detection of hepatic malignancies. Studies were performed with ¹³¹I labeled antibodies to CEA and/or CSAp; polyclonal, monoclonal and F(ab)₂ antibodies were used. Nontarget radioactivity was diminished by administration of ^99mTc reagents simulating nontumor distribution and use of a computer substraction method. In nine patients with confirmed liver neoplasms, radioimunodetection disclosed the foci of hepatic malignancies. In three patients with suspected liver neoplasms, the antibody studies were positive, but at this time have not been confirmed. X-ray computed tomography each disclosed mass lesions in five patients and magnetic resonance in three. These findings suggest that radioimmunodetection provides greater accuracy in the detection and localization of cancer than other diagnostic modalities currently used.This research was supported in part by NIH Grants CA37408, CA37409, CA37412, and CA39841     

Hepatic uptake of technetium-99m diisopropyl iminodiacetic acid (DISIDA) is not impaired by very high serum bilirubin levels

The hepatic clearance of Tc-99m labeled iminodiacetic acid (IDA) compounds is believed to be impaired in patients with severe hyperbilirubinemia. Competitive inhibition of hepatocyte uptake of IDA by bilirubin has been demonstrated in vitro, but not by clinical scintigraphy. We present a patient with Crigler-Najjar syndrome without evidence of hepatobiliary damage, who demonstrated normal uptake and excretion of Tc-99m DISIDA despite a serum indirect bilirubin level in excess of 30 mg/dl. It is therefore suggested that a markedly elevated serum bilirubin level per se does not inhibit hepatic uptake of Tc-IDA and does not preclude clinically useful scintigraphic examination.     

Clinical application of asialoglycoprotein receptor-mediated liver scintigraphy using 99mTc-DTPA-galactosyl-human serum albumin]

Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) is a new liver scintigraphy agent which binds to asialoglycoprotein receptors on the hepatocytes. Studies were performed in three normal volunteers and 19 patients with chronic liver diseases. Serial scintigrams and time-activity curves of heart and lever were obtained for 60 min following a single intravenous injection of 99mTc-GSA (1 mg/185 MBq). % Injected dose (%ID) in the blood at 60 min after injection and that in the liver were determined. Excellent hepatic images were obtained for 60 min in normal subjects, and neither blood pool image nor extrahepatic uptake was recognized. In the studies of patients, however, blood pools were also visualized in various degrees suggesting altered receptor quantity, although the livers were visualized clearly. The %ID in the blood at 60 min after the injection showed significant correlations with serum albumin levels (r = -0.741, p less than 0.0001), retention rates of ICG at 15 min (r = 0.855, p less than 0.0001), plasma disappearance rates of ICG (r = -0.760, p less than 0.0005), prothrombin times (r = -0.696, p less than 0.002), hepaplastin tests (r = -0.575, p less than 0.05), total bilirubin levels (r = 0.689, p less than 0.001) and Child Turcotte scores (r = 0.769, p less than 0.0001). Significant differences of %ID in both blood and liver were observed between normal subjects and patients in accordance with severities of the hepatic disorders. These results suggest that 99mTc-GSA liver scintigraphy is useful in evaluating the liver function.     

The diagnosis of acute complicated cholecystitis by Tc-99m sulfur colloid liver imaging

Increased hepatic activity surrounding the gallbladder fossa during Tc-99m SC liver imaging was observed. Subsequent Tc-99m IDA biliary imaging showed similar findings in the face of nonvisualization of the gallbladder--the classic "rim sign." Surgery confirmed the diagnosis of complicated acute cholecystitis. This case indicates that a rim sign may be seen with either Tc-99m SC or Tc-99m IDA imaging and may have the same diagnostic significance in both.     

Bidirectional transport of iminodiacetic organic anion analogues between plasma and hepatocyte

The kinetics of organic anions are well described and back-diffusion from hepatocyte to plasma is accepted. Although iminodiacetic (IDA) analogues, as organic anions, should also show bidirectional transport between hepatocyte and plasma, this has not been directly demonstrated heretofore. The aim of this study was to directly demonstrate back-diffusion and to quantify it in terms of its fractional rate constant. Kinetics of diethyl IDA were studied in three anaesthetised dogs in which femoral arterial and hepatic venous samples were obtained after injection of tracer into (a) a peripheral vein or (b) hepatic artery or portal vein. Arterial time-concentration curves were also compared between peripheral venous and either hepatic arterial or portal venous injections. Time-activity curves were recorded from regions of interest over the cardiac blood pool and peripheral hepatic parenchyma in 30 patients undergoing routine IDA hepatobiliary imaging with diethyl IDA or mebrofenin and fractional rate constants of clearance of IDA from the hepatocyte compared between compartmental and deconvolution analyses. After peripheral injection in dogs, there was an early arteriovenous concentration gradient across the liver indicating an hepatocyte extraction fraction in the three animals of 0.9, 0.8 and 0.6. The net extraction fraction decreased exponentially over 40 min. Time-concentration curves from hepatic vein and femoral artery were virtually superimposed following intrahepatic injections. Peripheral arterial curves, however, had different shapes according to whether injections were intrahepatic or peripheral, and were consistent with significant back-diffusion. In clinical studies, the blood disappearance curves were fitted as the sum of two exponentials and the liver curves as the difference of two exponentials (with rate constants denoted α₁ ^h and α₂ ^h). Based on compartmental analysis of the blood curves, the sum of the fractional rate constants of tracer movement from hepatocyte to bile canaliculus (k ₃₂) and to plasma (k ₁₂) was similar to and correlated with the rate constant, α, of the hepatocyte impulse response function (r=0.62, n=30, P<0.001). In contrast, α₁ ^h and α₂ ^h were respectively clearly greater and smaller than α. Moreover, neither of these hepatic rate constants correlated with α. Diffusion of IDA from hepatocyte to blood is significant and even in the presence of normal liver function accounts for about 50% of IDA transport out of the hepatocyte. It should be taken into account in pharmacokinetic studies based on either compartmental or deconvolution analysis. Received 23 January and in revised form 23 March 1998     

The role of Tc-99m IDA hepatobiliary and Tc-99m colloid hepatic imaging in primary biliary cirrhosis

To assess the presence of primary biliary cirrhosis, 15 patients at various histopathologic stages were studied by Tc-99m IDA hepatobiliary and/or Tc-99m colloid hepatic imaging. In the earlier stages (I and II), seven of eight patients (88%) showed uniform hepatic retention of Tc-99m IDA. Of seven patients in the same stage, however, four (57%) showed no abnormality on Tc-99m colliod imaging. In three of these four negative patients (75%), uniform hepatic retention of Tc-99m IDA was noted. In the later stages (III and IV), all seven patients showed decreased clearance with or without delayed tracer appearance in the intestine and prominent hepatic retention on Tc-99m IDA imaging; with Tc-99m colloid imaging there was enlargement of the spleen and increased activity in the spleen and bone marrow. Thus, Tc-99m IDA imaging is considered to be more useful in revealing this functional disorder at the earlier stage of primary biliary cirrhosis and in evaluating progression from an earlier to a later stage of disease. Tc-99m colloid imaging also effectively evaluated progression.     

Quantitative Evaluation of Liver Function with MRI Using Gd-EOB-DTPA

Objective

Gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) is a newly developed MR contrast agent. After intravenous injection, Gd-EOB-DTPA is gradually taken up by the hepatocytes and eventually excreted via the biliary pathway without any change to its chemical structure. Because of these characteristics, it can be used as a tracer for quantitative liver function testing. The purpose of this study is to develop a noninvasive method of quantitation of the hepatic function using Gd-EOB-DTPA through the deconvolution analysis.

Materials and Methods

Adult New Zealand white rabbits (n = 10, average body weight = 3.5 kg) were used in the present study. Hepatic injury was induced to by the intragastric administration of carbon tetrachloride (CCl4) three times a week for three weeks. Liver enzyme (aspartate aminotransferase, AST; alanine aminotransferase, ALT) levels and the plasma indocyanine green (ICG) retention rate 15 minutes after an intravenous injection of ICG (ICG R15), was checked before and after the three-week administration of CCl4. At the end of experimental period, an observer "blinded" to the treatment given the rabbits performed the histological examination. MRI studies were performed before and after the three-week administration of CCl4 on a 1.5 T scanner using a human extremity coil. After intravenous bolus injection of Gd-EOB-DTPA (0.3 mL of Gd-EOB-DTPA freshly prepared in 2.7 mL of normal saline) through the ear vein, the 250 axial single level dynamic MR images were obtained using a fast low angle shot (FLASH, TR/TE = 11/4.2 msec, flip angle = 15, acquisition time 1 second, slice thickness = 5 mm, matrix = 128×128, field of view = 120 mm) sequence with 1.5 sec time intervals. The time-intensity curves were obtained at the abdominal aorta and the liver parenchyma that was devoid of blood vessels. Deconvolution analysis of the aortic (input function) and hepatic parenchymal (output function) time-intensity curves was performed with a modified Fourier transform technique to calculate the hepatic extraction fraction (HEF). The presence and type of hepatic injury were determined by the histopathologic examination and statistical analysis of the changes of the hepatic enzyme levels, the ICG R15 and Gd-EOB-DTPA HEF values between the time before and after CCl4 administration with Wicoxon signed rank test. Correlation between the Gd-EOB-DTPA HEF and the change of the ICG R15 were analyzed with Pearson''s correlation coefficient.

Results

Histopathologic examination showed findings that were compatible with hepatic fibrosis caused by chronic liver injury. The initial blood biochemical studies before the administration of carbon tetrachloride showed that the mean AST and ALT levels were 39.8±5.2 IU/L and 59.1±11.7 IU/L, respectively. The AST and ALT levels increased to 138.4±50.5 IU and 172.0±71.6 IU/L, respectively, after the three week administration of CCl4. The ALT and AST levels were significantly increased after the three weeks of CCl4 administration (p = 0.018). The ICG R15 values were 4.47±2.08% and 19.43±3.98% before and after three-week administration of CCl4, respectively. The ICG R15 values were significantly increased after hepatic injury (p = 0.018). After normalizing the HEF as 100% in each rabbit before CCl4 administration, the deconvoluted curve after CCl4 administration revealed less hepatocyte extraction efficiency with a mean value of 77.7±3.6. There was a significant correlation between the HEF and changes of the ICG R15 by the Pearson correlation coefficient assessment (correlation coefficient = -0.965, p = 0.000).

Conclusion

The Gd-EOB-DTPA HEF could be calculated from deconvolution analysis of aortic and hepatic parenchymal time-intensity curves obtained by dynamic MRI. The Gd-EOB-DTPA HEF was well correlated with changes of the ICG R15, which is the most common parameter used in the quantitative estimation of the hepatic function. The Gd-EOB-DTPA HEF is a direct, noninvasive technique for the quantitative evaluation of liver function. It could be a promising alternative for the determination of noninvasive hepatic function in those patients with liver disease.     

中晚期肝癌根治术后介入放射学治疗的临床研究

报告153例中晚期肝癌根治术后行肝动脉内化疗栓塞的结果。所有患者于根治术后45～90天行介入治疗,两组共计治疗497次,其中单纯肝动脉内化疗灌注399次,化疗栓塞98次,平均每例行3.65次,最多12次。本组资料1、2、3年复发率为20.3％,44.4％,和55.6％,低于文献报告。其生存率1、2、3年分别为70.6％,60.8％,55.6％。本研究表明:外科切除十预防性肝动脉内化疗栓塞,可提高中晚期肝癌的生存率和降低术后复发率,是一种有效可取的术后治疗方法。     

In vivo MR tracking of mesenchymal stem cells in rat liver after intrasplenic transplantation

PURPOSE: To prospectively track in vivo in rats intrasplenically transplanted stem cells labeled with superparamagnetic particles by using magnetic resonance (MR) imaging. MATERIALS AND METHODS: The study was approved by the institutional Committee on Animal Research. Liver damage in 12 rats was induced with subcutaneous injection of carbon tetrachloride (CCl4). Intrasplenic transplantation of 6x10(6) rodent bone mesenchymal stem cells (BMSCs) with (n=6) and without (n=6) superparamagnetic particle Fe2O3-poly-L-lysine (PLL) labeling was performed via direct puncture. Cell labeling efficiency was assessed in vitro by using Prussian blue stain and an atomic absorption spectrometer. MR examinations were performed immediately before and 3 hours and 3, 7, and 14 days after transplantation. Liver-to-muscle contrast-to-noise ratios (CNRs) on T2*-weighted MR images obtained before and after injection were measured and correlated with histomorphologic studies. Statistical analyses were performed by using repeated-measures analysis of variance. RESULTS: Rat BMSCs could be effectively labeled with approximately 100% efficiency. Migration of transplanted labeled cells to the liver was successfully documented with in vivo MR imaging. CNRs on T2*-weighted images decreased significantly in the liver 3 hours after injection of BMSCs (P<.05) and returned gradually to the level achieved without labeled cell injection in 14 days. Histologic analyses confirmed the presence of BMSCs in the liver. The labeled cells primarily localized in the sinusoids of periportal areas and the foci of CCl4-induced liver damage. Quantitative analysis of Prussian blue-stained cells indicated gradual decrease of dye pigments from 3 hours to 3, 7, and 14 days after injection. No free iron particles were found in the interstitium or within hepatic microvessels. CONCLUSION: The rat BMSCs could be efficiently labeled with Fe2O3-PLL and the relocation of the labeled cells to rat livers after intrasplenic transplantation could be depicted at in vivo MR imaging.     

TIPS reduces hepatic asialoglycoprotein receptor concentration in healthy pigs

PURPOSE: Technetium-99m-labeled diethylenetriamine pentaacetic acid galactosyl human serum albumin (TcGSA), a new agent for liver scintigraphy, is selectively attached to asialoglycoprotein receptors on liver cell membranes. A direct correlation exists between asialoglycoprotein receptor concentration, [R]o and hepatic functional reserve. The purpose of this study was to determine the effects of transjugular intrahepatic portosystemic shunting (TIPS) on hepatic asialoglycoprotein receptor concentration in pigs without liver parenchymal disease. MATERIALS AND METHODS: TIPS was performed in eight pigs with use of a single 10-mm-wide x 68-mm-long Wallstent dilated to 10 mm. TcGSA dynamic imaging studies were performed before and twice after (7 and 14 days) TIPS. To be included in the study, pigs had to have a patent TIPS at 1 week of follow-up. Liver function tests were drawn parallel to the TcGSA studies. Liver biopsies were performed at 2 weeks when the animals were killed. RESULTS: Five of the eight pigs had open shunts at 1 week and were included in the study. There was a significant (P < .0001, Student t test) difference between the mean [R]o of the pre-TIPS studies ([R]o = 1.12+/-0.04 microM) and the mean of the post-TIPS studies at 7 days ([R]o = 0.40+/-0.04 microM) and 14 days ([R]o = 0.51+/-0.06 microM, P < .01). The only blood test that was abnormal after TIPS was ammonia (mean, 129.0+/-42.7). Liver biopsies were normal. CONCLUSIONS: TIPS reduces asialoglycoprotein receptor concentration in normal pigs.