Ikekubo K

Serum growth hormone-binding protein, insulin-like growth factor-I, and growth hormone in patients with liver cirrhosis.

We determined serum growth hormone-binding protein (GHBP), insulin-like growth factor-I (IGF-I), and growth hormone (GH) levels in patients with cirrhosis and in age-matched control subjects, and investigated their relationships. Serum GHBP levels in cirrhotic patients (14.6% +/- 3.9%) (means +/- SD) were significantly lower than those in normal subjects (20.4% +/- 4.7%). GHBP levels had positive correlations with cholinesterase (r = .58, P less than .001) and Normotest (r = .66, P less than .001), both of which represent liver function in cirrhotic patients. Basal GH levels in cirrhotic patients (range, 0.35 to 13.0 micrograms/L; median, 3.9 micrograms/L) were significantly higher than those in normal subjects (0.015 to 6.0 micrograms/L; 0.19 microgram/L). GHBP levels in cirrhotic patients correlated positively with IGF-I levels (r = .39, P less than .01), and negatively with GH levels (r = -.33, P less than .01). These results may indicate that the serum GHBP level reflects the number of hepatic GH receptors, and that the high basal GH level observed in cirrhotic patients is, at least in part, attributable to decreased clearance of GH by these receptors.

Compartmental analysis of asialoglycoprotein receptor scintigraphy for quantitative measurement of liver function: A multicentre study

A multicentre study on multicompartmental analysis of hepatic scintigraphy using technetium-99m labelled galactosyl serum albumin (GSA), which binds to the asialoglycoprotein receptor, was carried out at seven institutions in Japan. Seventy-four patients with liver disease received 3 mg (185 MBq) of99mTc-GSA by intravenous injection. Sequential scanning was performed 30 min after injection to obtain anterior images of the heart and liver, followed by single-photon emission tomography (SPET). The indices included in this analysis were hepatic blood flow (Q) and maximal receptor binding rate (Rmax), which showed a good correlation with semiquantitative ratio indices for99mTc-GSA, namely the retention rate in blood (HH15) and the hepatic uptake rate (LHL15).Q andRmax also showed a significant correlation with other measures of hepatic function. When patients were grouped according to the severity of chronic liver damage (hepatocellular functional damage),Q was reduced in the moderate and severe groups, whileRmax was reduced in proportion to the functional stage. Both parameters showed no inter-institution difference using analysis of co-variance with the functional stage as a co-variant. With regard to the hepatic uptake rate, anterior planar images and SPET images gave similar results forQ andRmax. Acquisition times of 15 or 30 min provided the same results. The multicopartmental model analysis permitted comparable results to be obtained at institutions using different gamma cameras, and is therefore considered a universally applicable method. These results indicate thatQ andRmax are useful general indices for evaluating the function reserve capacity of the liver.

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

SummaryAsialoglycoprotein 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<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.

[27] Synthesis and radiolabeling of galactosyl human serum albumin

Publisher Summary This chapter describes the procedures for the synthesis and radiolabeling of galactosyl human serum albumin (GSA). In addition, the radiochemical purity and stability as well as the biodistribution of technetium-99 m -labeled GSA in animals are presented in this chapter. The radioligand is commercially available in Japan and is actively used for the assessment of liver function, especially hepatic functional reserve by the concurrent use of a kinetic analysis system. It is expected that the usefulness of synthetic asialoglycoprotein analogs will continue to grow, not only for diagnosis of receptor function either by nuclear medicine techniques or by other techniques such as magnetic resonance imaging, but also for therapy of liver diseases.

Accumulation of Tc-99m methylene diphosphonate in calcified metastatic lesions of the liver from colonic carcinoma. Comparison with calcification on X-ray computed tomogram.

Abnormal accumulation of Tc-99m MDP in two metastatic lesions of the liver was observed in a patient with resected colon carcinoma. Single-photon emission computed tomography (SPECT) revealed characteristic marginal accumulation of Tc-99m MDP in both of those metastatic lesions. X-ray CT showed the corresponding marginal calcification in one of the metastases, but no apparent calcification was observed in the other lesion. Two months later, however, the latter also became calcified on x-ray CT. These findings suggest that the accumulation of Tc-99m MDP in the present case is strongly related to the calcium deposition and that Tc-99m MDP may accumulate in a calcified metastatic lesion before the calcification appears on x-ray CT.

Measurement of functioning hepatocyte mass via [99mTc]galactosyl-neoglycoalbumin.

Technetium-99m-galactosyl-neoglycoalbumin (TcNGA) is a synthetic radiolabeled ligand specific for hepatic binding protein (HBP), a receptor that resides exclusively on hepatocytes.In vivo measurement of receptor concentration was obtained via kinetic analysis of liver and blood time-activity data obtained during the hepatic clearance of intravenously administered TcNGA. The purpose of this study was to assess receptor concentration as a measure of the functioning hepatocyte mass. Therefore, TcNGA and dualinjection indocyanine green maximal removal rate (ICG Rmax) studies were performed on nine patients with hepatic cirrhosis associated or not with hepatocellular carcinoma. Receptor concentration was compared with ICG Rmax, which is a validated method for the estimation of the functioning hepatocyte mass. The correlation coefficient was 0.76 (P=0.017). It is concluded that HBP concentration ([HPB]o) as measured by functional imaging is a measure of functioning hepatocyte mass. This implies that measurement of an individuals receptor concentration by using nuclear medicine techniques provides an objective index of hepatic functional mass and supports attempts to rigorously evaluate [HBP]o for its clinical efficacy.

A Case Report of Hashimoto's Disease with Anti-Thyroxine Autoantibody

In one case of untreated Hashimotos disease, serum thyroxine (T4) value by radioimmunoassay (RIA) was significantly lower than that by competitive protein binding analysis (CPBA). The discrepancy was found to be due to the presence of antithyroxine autoantibody in the serum. This phenomenon was considered to be of practical importance in interpreting the T4 value by RIA in cases with autoimmune thyroid diseases. The patient was 59-year-old woman with a 30-year history of goiter. A diagnosis of Hashimotos thyroiditis had been established by open biopsy of the thyroid ten years ago. The patient was judged to be euthyroid on the basis of clinical and laboratory evaluation (mean serum T4 by CPBA (Tetrasorb and Tetratab kit), 5.0 mug/100 ml; serum T3, 165 ng/100 ml; T3 resin uptake, 31.8%; and serum TSH, 2.0 muU/ml). TBG binding capacity was 24 mug/100 ml. Anti-thyroglobulin antibodies (anti-Tg), once positive ten years before, was negative at this time. But the mean T4 in the serum measured by T4 RIA and RIA-Mat T4 kit were 1.7 and 2.9 mug/100 ml, respectively. Recovery of the T4 added to the patients serum evaluated by RIA-Mat T4 kit, was 71.2%, although the recovery using a control serum was 108%. Binding of 125I-T4 to the serum or fractions of the serum was studied by using polyethylene glycol (PEG) method, column chromatography, and double antibody precipitation. The results were as follows: 1) The binding of 125I-T4 to the patients serum was detected by using RIA kit system without addition of anti-T4 serum. 2) On Sephadex G-200 chromatography of 125I-T4 incubated with the serum or the rabbit anti-T4 antibody in the presence of ANS, an early radioactive peak was observed by using the patients serum as in the case of the anti-T4 antibody. When the serum after thermal inactivation of TBG, was incubated with 125I-T4, and was applied to the Sephadex G-200 column, a radioactive peak was observed in the area where 7S fraction was detected by protein peak. 3) The binding of 125I-T4 to the patients IgG was 9.0% by using double antibody method when the binding to a control IgG was 0.5%. 4) The binding of 125I-T4 to IgG fractions was also proved by PEG method. 5) The binding of 125I-T4 was competitively inhibited by the addition of unlabeled T4. The affinity constant was 1.9 X 10(8) L/mol and its binding capacity was 0.8 mug/100 ml serum. From these data this T4 binding IgG was considered to be anti-T4 autoantibody. The cross reaction with T3 was approximately 8.3%. MIT and DIT did not displace labeled T4 when tested in amounts varying from 0.1 to 100 ng/assay. By using the paper electrophoresis, the binding of 125IT4 to the serum or IgG was not detectable. Therefore this method was considered unsuitable for detecting such anti-T4 antibody. As we couldnt find any significant binding of 125I-T4 to sera in 37 other patients with Hashimotos disease by using the PEG method, the incidence of this phenomenon was considered to be low...

A follow-up study using iodine-131 metaiodobenzylguanidine imaging in a patient with neuroblastoma.

A new radiopharmaceutical, I-131 metaiodobenzylguanidine (I-131 MIBG) was used to determine the location and to follow-up tumors in a 13-month-old girl with neuroblastoma. I-131 MIBG imaging revealed both a primary abdominal tumor and a distant metastatic orbital tumor. Follow-up study with I-131 MIBG imaging demonstrated significant resolution of tumors after external radiotherapy and chemotherapy. I-131 MIBG imaging is a simple, safe, and specific method of determining the location of tumors and also is clinically useful in the evaluation and management of patients with neuroblastoma.

The Development of a Solitary Toxic Thyroid Nodule Following Graves' Disease

A 52-year-old woman developed a toxic, solitary, autonomously functioning thyroid nodule four years after antithyroid drug treatment for Graves disease. When she was initially seen, a thyroid scan showed the homogeneous enlargement of both lobes with increased uptake. Graves disease was diagnosed and the patient was treated with methimazole. Thyroid function was well-controlled with medication for 18 months, after which the patient stopped taking the drug for three years. Four years after Graves disease was diagnosed, the patient again showed symptoms of hyperthyroidism. The etiology was a toxic, autonomously functioning nodule.