Biomedical subjects

P Angelberger

Publications and source records attributed to P Angelberger.

At least 73 records · Page 4Linked to original sources

PubMed1992

Aspirin abolishes the decreased low-density lipoprotein (LDL) entry into the rabbit arterial wall induced by the calcium channel blocker isradipine.

After deendothelialization and experimentally induced hypercholesterolemia in rabbits, an increased LDL entry into the vascular wall can be monitored using radiolabelled LDL. In male rabbits aged 6 months the abdominal aortic endothelium was removed by a Fogarty catheter. The animals fed a 1% cholesterol supplemented diet were treated either with isradipine (0.3 mg/kg/daily) (n = 36) alone or in combination with aspirin (5 mg/kg/daily) (n = 36) for four weeks. Thirty-six animals served as controls. 1, 3, 6, 12, 24 and 48 hours prior to sacrificing, 10 microCi 125I-LDL was administered intravenously to six rabbits in each group. The LDL entry was quantified in the abdominal aorta according to morphologically assessed type of surface lining. Aortic cholesterol content was assessed by Sudan-III staining and quantitative determination. Endothelialized segments exhibited a significantly (p less than 0.05 - p less than 0.001) lower LDL uptake as compared to re- or deendothelialized segments. The LDL entry was significantly lower with isradipine treatment than in controls. In parallel the cholesterol content decreased and the Sudan-III-positive areas were smaller in size. This beneficial effect as well as that on aortic lipid content was abolished by a pretreatment with aspirin. While in the isradipine-treated animals PGI2 synthesis was significantly (p less than 0.01) enhanced, it was almost completely blocked by aspirin. These findings indicate that the benefit of reduced LDL entry caused by isradipine may be mediated by an increased endogenous PGI2 synthesis.

Animals↗

PubMed1992

Uptake mechanism of technetium-99m-d, 1-HMPAO in cell cultures of the dissociated postnatal rat cerebellum.

The accumulation and retention mechanisms of 99mTc-d, 1-hexamethylpropyleneamine oxime (99mTc-d, 1-HMPAO) were investigated in cultures of the dissociated rat cerebellum. Our experiments indicate a linear dependency of the uptake on incubation time and on the concentration of the radioligand. Upon chloroform extraction and distribution between the lipophilic and the hydrophilic phases, we located 69.1% of the retained radioactivity in the hydrophilic phase, 24.1% in a bound state and 6.8% in the lipophilic phase. The water-soluble, unbound radioactive contents of the cultures were identified as 99mTcO4- by HPLC analysis. Treatment of cultures with diethyl maleate (DEM) inhibited the accumulation of radioactivity along with a reduction of the GSH contents of the cultures. However, even in the absence of GSH, significant amounts of radioactivity were accumulated. DEM reduced the radioactive contents of cultures predominantly by diminishing the aqueous phase of the chloroform-extracted material. By contrast, the metabolic state, manipulated by treating the cultures with oligomycin B or 2,4-dinitrophenol, had no significant effect on the accumulation of radioactivity. Our experiments suggest two major mechanisms for the retention of radioactivity following the exposure of neuronal tissue to 99mTc-d, 1-HMPAO: Conversion of the lipophilic complex to the hydrophilic product, 99mTcO4-, and binding to non-diffusible cell components.

2,4-Dinitrophenol↗

PubMed1991

Lymphoscintigraphy with 123I-labelled epidermal growth factor.

We have used 123I-labelled epidermal growth factor (EGF) scans to study 14 patients with advanced cervical cancer. Abnormal lymph node imaging was seen most clearly 6-8 h after the injection and revealed abnormal uptake by pelvic lymph nodes in 11 patients. 4 of these 11 had abnormal computerised tomographic and ultrasound scans; in the other 7 conventional radiology did not confirm the presence of disease.

Carcinoma, Squamous Cell↗

PubMed1991

Low density lipoprotein labelling characterizes experimentally induced atherosclerotic lesions in rabbits in vivo as to presence of foam cells and endothelial coverage.

The entry of autologous iodine-125 low density lipoprotein (125I-LDL) into the aortic wall in rabbits was measured. After abdominal endothelium abrasion with a Fogarthy catheter the animals were fed a 1% cholesterol-supplemented diet for 4 weeks. The animals were killed 1-48 h after administration of 25 muCi 125I-LDL. Local entry of radiolabelled LDL was estimated and correlated to endothelial surface lining and foam cell content, both controlled morphologically. Endothelialized segments showed the lowest entry of 125I-LDL, the maximum uptake was reached at around 8 h. In de-endothelialized segments the entry was higher and the peak later (12 h), while in re-endothelialized segments a continuous increase in 125I-LDL entry up to 48 h was measured. Number and extent of foam cells correlated with the entry of LDL. The data indicate the usefulness of LDL radiolabelling for qualitative in vivo information on surface lining and foam cell content.

Animals↗

PubMed1991

Autologous low-density lipoprotein labelling allows characterization of human atherosclerotic lesions in vivo as to presence of foam cells and endothelial coverage.

The monitoring of local vascular kinetics after injection of autologous radiolabelled low-density lipoprotein (LDL) allows characterization of human atherosclerotic lesions as to the presence of foam cells and the quality of endothelial coverage. The following evidence exists: (1) dynamic imaging reveals two types of visual LDL accumulation in the vascular bed, one increasing, becoming visible sometimes only as late as after 24 h, and the other one appearing very early on, but decreasing with time; (2) the accumulation of iodine-123 LDL or iodine-131 LDL in the vascular bed shows three major types of local kinetic curves, which correlate with scintigraphic findings; (3) the accumulation of radiolabelled LDL in the vascular bed of humans in vivo is similar to its uptake in de- and re-endothelialized vessels of experimental animals using 125I-LDL; (4) morphological control in endarteriectomy samples confirms the hypothesis that this promising new approach may for the first time allow the in vivo monitoring of preclinical lesions in humans.

Adult↗

PubMed1991

Effect of prostaglandin E1 on low density lipoprotein apo-B-receptor binding in human, rat and swine liver in vitro.

The effect of PGE1 on low density lipoprotein (LDL) apo-B-receptor binding was examined in human, rat and swine liver. Autologous LDL (for humans and swines) and homologous LDL (for rats) were isolated by ultracentrifugation and labelled with 123I using Iodogen followed by purification with dialysis. LDL-concentrations of 0.1-6 micrograms protein/ml were used for direct binding assays investigating the specific binding of labelled LDL in presence of increasing PGE1-concentrations (100 pM to 100 microM). In separate experiments the effect of PGE1 on displacement of specifically bound 123I-LDL by unlabelled ones was studied. The binding capacities estimated by Scatchard analysis were similar for human and rat liver LDL-apo-B-receptor binding, however, swine liver exhibited a significantly (p less than 0.001) lower binding capacity for 123I-LDL. PGE1 significantly (p less than 0.01-0.001) increased the amount of 123I-LDL specifically bound to the liver apo-B-receptors and the binding affinity in all liver preparations of the 3 species in a dose-dependent manner. PGE1 also significantly increased competition of unlabelled LDL for 123I-LDL bound to its specific apo-B-receptors in a dose-dependent manner (p less than 0.01-0.001) with an ED50 of 123 +/- 64 nM for human liver, 901 +/- 102 nM for rat liver obtained during anaesthesia, 74 +/- 23 nM for rat liver obtained after decapitation and 941 +/- 121 nM for swine liver. In human liver iloprost (ED50 = 876 +/- 53 nM) and PGI2 (ED50 = 52 +/- 12 microM) were less effective than PGE1, PGE2 had no effect on LDL-induced competition. It is concluded that PGE1 renders LDL more sensitive for apo-B-receptor binding suggesting a potential hypolipidemic action of PGE1.

Adult↗

PubMed1991

Comparison of different methods for LDL isolation and radioiodination on liver LDL receptor binding in vitro.

Lipoproteins were isolated either by immunoaffinity chromatography (LDL and VLDL) or ultracentrifugation (LDL). Purified lipoproteins were labeled with 123I using either Iodogen or iodine-monochloride (IC1) each followed by purification with gel-chromatography or dialysis (total of 4 combinations). Lipoprotein-concentrations of 0.1-6 micrograms protein/mL were used for direct binding assays investigating the specific binding of labeled lipoproteins (in the presence of a 50-fold excess of unlabeled lipoproteins) to human liver apo-B, E-receptors. In separate experiments displacement of bound 123I-lipoproteins (labeled by the methods mentioned) by unlabeled ones was studied. The binding capacities estimated by Scatchard analysis were similar to each other (141-163 ng protein bound/mg liver plasma membrane protein) independent from the method used for isolation and labeling. Also the affinity constants were very similar and ranged from 0.9 to 1.7 micrograms protein/L. It is concluded that immunoaffinity chromatography or ultracentrifugation for isolation of lipoproteins and the Iodogen or IC1-method for radiolabeling can be recommended to be equally good for in vitro receptor investigation.

Adult↗

PubMed1991

Dopamine D2 receptor imaging with SPECT: studies in different neuropsychiatric disorders.

The purpose of the present study is to visualize and quantify dopamine D2 receptors in the living human brain using an 123I-labeled ligand and the single photon emission computerized tomography (SPECT) technique. S-(-)-Iodobenzamide [S-(-)-IBZM] has been shown to be a highly selective ligand with high affinity for D2 receptors in experimental studies. Five millicuries (185 MBq) of 123I-labeled S-(-)-IBZM was administered intravenously to 12 control subjects, 22 parkinsonian patients under L-Dopa therapy, 12 parkinsonian patients without L-Dopa, 10 unmedicated patients with Huntington's disease, and 12 patients under different neuroleptics. Data collection with a rotating double-head scintillation camera started 1 h after injection and lasted for 50 min. In a semiquantitative approach, a ratio was calculated between mean counts per pixel in the striatum and a region in the lateral frontal cortex, which was 1.74 +/- 0.10 in the control group. A marked reduction of this ratio was found in patients with Huntington's disease (1.38 +/- 0.12; p = 0.0001), no significant changes in untreated parkinsonian patients (1.67 +/- 0.14), but a reduction in L-Dopa-treated cases (1.59 +/- 0.13; p = 0.0014). A curvilinear relationship was found between total daily dose of neuroleptics and the reduction of this ratio. Estimated receptor blockade under full neuroleptic treatment was 75-80%. S-(-)-IBZM binding was reduced with increasing age (p less than 0.01). Specific binding was reduced markedly when the racemic mixture of IBZM was used, and no specific binding was seen with the R-(+)-isomer, demonstrating the stereoselectivity of IBZM binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Isradipine, a calcium-entry blocker, decreases vascular [125-I]low-density lipoprotein entry in hypercholesterolemic rabbits.

In 72 male rabbits aged 6 months, the endothelium of the abdominal aorta was abraded by a Fogarthy catheter. The animals were then fed a 1% cholesterol-supplemented diet for 4 weeks. In addition, half of the animals were treated for the entire period with isradipine (0.3 mg/kg daily), a dihydropyridine calcium antagonist; the other 36 animals served as controls. One hour and 3, 6, 12, 24, and 48 hours before the animals were killed, [125-I]low-density lipoprotein (LDL 10 microCi) was administered intravenously (i.v.) to six animals in each group. The [125-I]LDL entry was quantified in the abdominal aorta according to the type and presence of endothelial lining. Isradipine significantly reduced the [125-I]LDL entry at most time intervals. In parallel, an increase in vascular prostaglandin (PGI2) synthesis was noted, which might be the underlying mechanism for the decreased LDL entry.

Animals↗

PubMed1991

Functional liver imaging with 99Tcm-galactosyl-neoglycoalbumin (NGA) in alcoholic liver cirrhosis and liver fibrosis.

Synthesis of 99Tcm-galactosyl-neoglycoalbumin (99Tcm-NGA), a recently described new radioligand with high specificity for hepatic binding protein (HBP), a galactose-residue specific receptor on hepatocytes, was carried out by covalent coupling of 2-imino-2-methoxyethyl-1-thio-beta-D-galactopyranoside to the primary amino groups of human serum albumin. NGA was purified by ultrafiltration and size exclusion high-pressure liquid chromatography (HPLC). Using a computer-based simulation program, time-activity data for the liver and precordium, blood radioactivity 2 min after i.v. injection of the radioligand, the association constant of 99Tcm-NGA-binding to HBP measured on human liver biopsies in vitro, and other patient-related parameters were put into a five-state non-linear model describing the pharmacokinetics of 99Tcm-NGA. By fitting the parameters of the model iteratively to the experimental data, an estimate of HBP concentration in the liver and of total liver blood flow was obtained. Using this model we studied 32 patients (53 +/- 11 years) with different clinical stages of alcoholic liver cirrhosis. Child B and Child C stage cirrhotic patients had a lower HBP concentration in the liver compared to control individuals (0.96 +/- 0.21 mumol l-1). The group with the most advanced cirrhosis (Child C stage) had a significantly lower HBP concentration (0.27 +/- 0.15 mumol l-1) than Child A patients (0.66 +/- 0.21 mumol l-1; P less than 0.01) and Child B patients (0.53 +/- 0.18 mumol l-1; P less than 0.05). In four patients with biopsy-proven liver fibrosis (0.84 +/- 0.20 mumol l-1) no difference in receptor concentration from normal individuals was estimated. Changes in liver blood flow were not significant between the groups. A direct comparison of HBP concentration estimated in vivo by 99Tcm-NGA functional imaging and HBP concentration measured in vitro on a surgically removed liver biopsy specimen from the same patient with a normal liver and liver cirrhosis showed good matching of these two values. The results suggest that in vivo estimation of HBP concentration in the liver by 99Tcm-NGA functional imaging might be a suitable method for determining liver cell mass.

Adult↗

PubMed1991

Dynamic SPECT in two healthy volunteers to determine the optimal time for in vivo D2 dopamine receptor imaging with 123I-IBZM using the rotating gamma camera.

Dynamic SPECT was performed in two healthy male volunteers with a single slice brain dedicated camera (Strichman Medical Equipment 810, first study) and a rotating gamma camera (Siemens Dual Rota ZLC37, second study) to obtain information about the optimal imaging time for the dopamine D2 receptor specific ligand 123I-(S)-(-)-2-hydroxy-3-iodo-6-methoxy-N[(1-ethyl-2-pyrrolidinyl) methyl]-benzamide (123I-IBZM). Count rates in the basal ganglia and in several cerebral cortical regions were used to define specific and aspecific binding, respectively. On the basis of the first study, 90-150 min seemed the optimal time for rotating gamma camera 123I-IBZM-SPECT. On the basis of the second study the optimal period was considered to be 60-120 min. It is recommended to apply the same imaging time after injection in a protocol to all patients and volunteers as otherwise a comparison may not be reliable.

Adult↗

PubMed1991

Prostaglandin E1 decreases the low-density-lipoprotein entry into rabbit arterial wall.

1. In 72 male rabbits fed a 1% cholesterol supplemented diet the effect of a 4 weeks daily infusion of prostaglandin E1 (PGE1, 20 micrograms kg-1 min-1 over 2 h) on [125I]-low density lipoprotein (LDL) accumulation (10 microCi; 0.5 mg protein ml-1) was examined versus sham-treatment after removal of the endothelium of the abdominal aorta by a Fogarthy catheter. 2. The uptake of [125I]-LDL was significantly (P less than 0.01) higher in endothelium-free aortic segments (showing the highest peak maximum at around 12 h after 125I-injection) as compared to aortic segments with endothelium intact (showing the lowest uptake of [125I]-LDL with the peak maximum at 48 h, last control time). Segments with the endothelium restored showed a similar LDL-retention curve to segments with endothelium however, being again significantly (P less than 0.01) higher. 3. PGE1-treatment caused reduction in LDL-accumulation, being significantly (P less than 0.001) pronounced in segments without endothelium and in segments with endothelium restored. 4. The findings indicate a beneficial effect of PGE1 in lipid metabolism by decreasing the LDL-influx into the arterial wall in-vivo.

Alprostadil↗

PubMed1991

Evaluation of somatostatin receptors in human cancer.

The binding of 123I-Tyr-3-octreotide (SDZ-204-090; specific activity 1 mCi/nmol), a new somatostatin-receptor binding radiopharmaceutical, to human tumour membrane fractions was evaluated in presence of unlabeled Tyr-3-octreotide and octreotide (SMS-201-995; Sandostatin). Tumour tissue was obtained intraoperatively from 15 patients with different endocrine tumours (insulinoma, carcinoide, phaechromocytoma, hypophysal adenoma) and breast cancer. In equilibrium experiments, membrane fractions (200 micrograms protein/ml) were incubated with increasing concentrations of 123I-Tyr-3-octreotide (0.03-30 nM) in presence or absence of 5 microM of unlabeled agonist. Binding capacities ranged from 1-20 pmol/mg protein (Kd 4-100 nM). The IC50 values (2.5-112 nM versus 0.02-69 nM) were different for the octreotide and Tyr-3-octreotide indicating that octreotide was the better competitor as Tyr-3-octreotide for 123I-Tyr-3-octreotide binding sites. In ductal breast cancer high numbers of in vitro binding sites for the radiolabel were found. In initial clinical studies 123I-Tyr-3-octreotide was i.v.-injected (3 mCi) to 5 acromegaly patients with hypophyseal adenomas. Following rapid uptake by the liver, positive tumour imaging was obtained in 3 patients which correlated to computer tomographic findings. Positive images were obtained just some minutes after injection. Our results support recent data suggesting that the 123I-Tyr-3-octreotide would be a suitable receptor-radiopharmaceutical for the localization of endocrine tumours.

Adenoma↗

PubMed1991

Lymphoscintigraphy using epidermal growth factor as tumour-seeking agent in uterine cervical cancer.

Fourteen patients suffering from advanced inoperable cervical cancer were investigated by planar scintigraphy after subcutaneous administration of a radiolabelled (I-123) epidermal growth factor (EGF). The objective of the study was to test whether labelled EGF concentrates in lymph node metastases of squamous cell cancer of the cervix uteri. Scintigraphic results were correlated with the gynecological findings, computed tomography (CT), ultrasound (US) and in two patients with histology. A series of scintigrams were performed up to 24 hours post injection. Slight activity in liver and kidneys was found already 30 min after s.c. injection of EGF. Optimal imaging quality for the lymphatics was obtained at 6-8 hours post injection. Accumulation in the pelvic lymph nodes was documented by the region of interest technique (ROI). Lymph nodes of the inguinal and iliac communis region were marked in all cases. Due to this, accumulation of EGF could not be called selective. In 11/14 patients hot spots were correlated to other pelvic lymph nodes. In 4/11 patients with positive EGF-scanning metastatic disease was confirmed by CT scan and/or US examination. 2/11 patients underwent a Probatoria operation. The respective histological reports confirmed our scintigraphic results. In conclusion, labelled EGF did not fulfil our theoretical expectations of excellent accumulation in lymph node metastases and cannot at present be recommended for routine clinical use.

Carcinoma, Squamous Cell↗

PubMed1991

123I-tyrosine-(A14)-insulin: preparation and preliminary clinical studies.

Insulin was radioiodinated with 123I (123I-tyrosine-(A14)-insulin) to a specific activity of 1 micrograms/mCi, corresponding to 0.025 I.U. of insulin/mCi. This preparation was used for in vitro binding experiments with adipose tissue, showing active binding to the two subunits of the known insulin receptor. In a preliminary clinical investigation, 5 adipose patients with (n = 2) and without (n = 3) diabetes mellitus Type II, were subject to in vivo injection of the same radiolabeled product using 3 mCi/patient. During the first minutes of dynamic imaging, the liver was the major organ of tracer uptake in all patients. Furthermore, the pancreas, and in one patient the kidneys, were visualised. Further studies on insulin in vivo kinetics and quantification are under way.

Diabetes Mellitus↗

PubMed1991

Recent developments in receptor binding radiopharmaceuticals.

The stereoselective and saturable binding between receptor and ligand molecules plays an important role in many biological processes. Therefore ligand-receptor interactions have been increasingly studied in recent years by means of radionuclide labelled ligand molecules of high radiochemical purity and high specific activity. This contribution describes radiochemical development work of such radioligands performed at the Austrian Research Centre Seibersdorf in recent years: Tc99m-Neo-Galacto-Albumin was prepared as ligand for the Hepatic Binding Protein receptor, I-123-Low Density Lipoprotein (LDL) for LDL-receptors in the liver. Since LDL is involved in the origin of atherosclerosis it was subsequently labelled with Tc99m and In-111 as well. A pyrrolidine-methyl-benzamide derivative was separated into its stereoisomers and the active form labelled with I-123. It exhibited specific uptake in Dopamine D-2 receptor containing brain tissue. A benzazepine derivative was likewise labelled with I-123 as potential ligand for D-1 receptors.

Albumins↗

PubMed1991

Quantification of human hepatic binding protein (HBP) via 99mTc-galactosyl-neoglycoalbumin (NGA) liver scintigraphy.

99mTc-galactosyl-neoglycoalbumin (99mTc-NGA) was synthesized by covalent coupling of 2-imino-2-methoxyethyl-1-thio-beta-D-galactopyranoside to the primary amino groups of human serum albumin. Injection of 99mTc-NGA (150 MBq; 3.5 mg (= 50 nmol)/ml demonstrated the liver to be the exclusive site of tracer-uptake. Simulation of 99mTc-NGA-kinetics allowed quantification of binding to the hepatic binding protein (HBP). Using this model we studied 250 patients with various liver disease. In alcoholic liver cirrhosis such patients with Child B and Child C stage cirrhosis had a lower HBP-concentration in the liver compared to control individuals (0.85-1.2 mumol/l). The group with the most advanced cirrhosis (Child C stage) had a significantly lower HBP-concentration (0.20-0.45 mumol/l) than Child A patients (0.60-0.85 mumol/l; p less than 0.01) and Child B patients (0.45-0.60 mumol/l; p less than 0.05). In patients with biopsy proven liver fibrosis (0.80-1.22 mumol/l) no difference in receptor concentration to normal individuals was estimated. Patients with recently diagnosed acute viral hepatitis underwent repeated 99mTc-galactosyl-neoglycoalbumin (NGA) scanning of the liver during the course of the disease. Return of liver function tests to normal values was associated with an increased hepatic imaging size as well as increase in HBP-concentration (up to a 3-fold of initial concentration). In patients exhibiting a prolonged course of the disease changes in NGA-kinetic data were borderline and the hepatic image size unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

PubMed1991

Indium-111-labeled low-density lipoprotein binds with higher affinity to the human liver as compared to iodine-123-low-density-labeled lipoprotein.

The interaction of 111In-low-density lipoprotein (LDL) and 123I-LDL with human liver-plasma membranes was investigated and compared. LDLs were isolated by sequential ultracentrifugation and radiolabeled either with 123I (using lodogen or iodine-monochloride) each followed by purification with gel-chromatography or dialysis) or 111In (using cyclic DTPA-anhydride). LDL concentrations of 0.1 to 32 micrograms protein/ml were used for direct binding assays investigating the specific binding of labeled LDL (in the presence of a 50-fold excess of unlabeled LDL) to human liver apoB-receptors. In separate experiments, displacement of bound 111In-(123I)-LDL by unlabeled LDL was studied. Human liver plasma membranes bound 239 +/- 26 ng protein of 111In-LDL/mg protein and 148 +/- 18 ng protein of 123I-LDL/mg protein specifically (p less than 0.001). The corresponding dissociation constants were 0.6 +/- 0.2 and 1.2 +/- 0.7 micrograms protein/ml, respectively (p less than 0.001). The capacity of unlabeled LDL to displace bound 111In-LDL was four times higher than that for 123I-LDL (IC50: 1.7 +/- 0.7 versus 7.7 +/- 1.0 micrograms protein/ml). No significant differences among the different methods of iodination of LDL were found. The findings show that 111In-labeled lipoproteins might be a better ligand for lipoprotein-receptor binding studies as compared to radioiodinated lipoprotein products.

Adult↗