Biomedical subjects

P Angelberger

Publications and source records attributed to P Angelberger.

At least 55 records · Page 3Linked to original sources

PubMed1995

Vasoactive intestinal peptide receptor scintigraphy.

UNLABELLED: This study presents the biodistribution, safety and absorbed dose of 123I-VIP administered to 18 patients with intestinal adenocarcinomas or endocrine tumors. METHODS: To achieve high-specific activity, 123I-VIP was purified by HPLC. Following intravenous administration of 123I-VIP (172 +/- 17 MBq (4.65 +/- 0.5 mCi); < 300 pmole ( < 1 microgram)/patient), sequential images were recorded during the initial 30 min. Thereafter, whole-body images were acquired in anterior and posterior views at various time points. Dosimetry calculations were performed on the basis of gamma camera data, urine, feces and blood activities. RESULTS: After injection of labeled peptide, the lung was the primary site of 123I-VIP uptake. Peak lung activity represented 40% +/- 7% of the injected dose at 0.7 hr and declined to 21% +/- 7% at 3.5, to 14% +/- 3% at 7 and to 8% +/- 4% 22 hr postinjection. Radioactivity was excreted into the urine and amounted to 37% +/- 16% of the injected dose within 4, 68% +/- 12% within 8, 82% +/- 16% within 16 and 93% +/- 8% within 24 hr postinjection. The mean effective half-life of 123I-VIP in the lungs was 2.2 and 6 hr in the urinary bladder. The highest radiation absorbed doses were calculated for the lungs [67 muGy/MBq (248 mrad/mCi)], urinary bladder [77 muGy/MBq (284 mrad/mCi)] and thyroid gland [104 muGy/MBq (386 mrad/mCi)]. The effective dose was 28 muSv/MBq (104 mrem/mCi). CONCLUSION: HPLC-purified 123I-VIP shows favorable dosimetry and is a safe and promising peptide tracer for localization of tumors expressing receptors for VIP.

Adenocarcinoma↗

PubMed1995

Technetium-99m-galactosyl-neoglycoalbumin combined with iodine-123-Tyr-(A14)-insulin visualizes human hepatocellular carcinomas.

UNLABELLED: Human hepatocellular carcinoma (HCC) is the most frequent primary hepatic malignancy and its diagnosis by conventional methods is still difficult. We hypothesized that the expression of specific receptors could possibly be used to improve in vivo localization of HCC with specific receptor-based radioligands. METHODS: In initial in vitro studies, receptor binding of 99mTc-galactosyl-neoglycoalbumin (99mTc-NGA) and 123I-Tyr-(A14)-insulin to HCC was investigated. Scintigraphy was performed in 45 patients with histologically confirmed HCC using either 99mTc-NGA (75-150 MBq; 25-50 nmole, n = 27) and/or 123I-Tyr-(A14)-insulin (100-150 MBq; 7.5-10 micrograms, n = 30). RESULTS: HCC (1256 +/- 290 pmole bound/mg protein, Kd = 3.4 +/- 2.9 nM) expressed a 1000-fold higher number of specific receptors for 123I-Tyr-(A14)-insulin compared to normal liver tissue (2.4 +/- 0.8 pmole bound/mg protein, Kd = 4.2 +/- 2.4 nM), whereas HCC did not express receptors specific for 99mTc-NGA. All HCC lesions were identified as cold spots after injection of 99mTc-NGA, whereas 123I-Tyr-(A14)-insulin accumulated in these lesions, indicating HCC-to-normal liver ratios of 1.6 +/- 0.4 in the mean. Subtraction images obtained from planar studies visualized 123I-Tyr-(A14)-insulin in HCC lesions detected by 99mTc-NGA as cold spots. CONCLUSION: This hepatocyte receptor-specific, double-tracer method using 99mTc-NGA and 123I-Tyr-(A14)-insulin could become clinically useful in the diagnosis of HCC.

Aged↗

PubMed1994

Vasoactive intestinal peptide-receptor imaging for the localization of intestinal adenocarcinomas and endocrine tumors.

BACKGROUND: Intestinal adenocarcinomas and various endocrine tumors express large numbers of high-affinity receptors for vasoactive intestinal peptide (VIP). We have evaluated the usefulness of scanning with VIP labeled with iodine-123 for tumor localization in patients with gastrointestinal tumors. METHODS: Radioiodinated VIP was purified by high-pressure liquid chromatography and administered as a single intravenous bolus injection (300 pmol [1 microgram]). Scanning with radiolabeled VIP was compared with computed tomography and scanning with somatostatin analogues in 79 patients with colorectal cancer, pancreatic carcinoma, gastric cancer, carcinoid tumor, or insulinoma. RESULTS: Visualization of gastrointestinal tumors and metastases was obtained with radiolabeled VIP. Binding of the labeled peptide by primary tumors and metastases was visible shortly after the injection and was still demonstrable at 24 hours. In patients with colorectal adenocarcinomas, primary or recurrent tumors were visualized in 10 of 10, liver metastases in 15 of 18, lung metastases in 2 of 3, and lymph-node metastases in 4 of 4. Primary pancreatic adenocarcinomas were visualized by imaging in 10 of 12 patients, and liver metastases were seen in 7 of 7. Primary or recurrent gastric adenocarcinomas were visualized in 5 of 5 patients, and liver metastases were seen in 2 of 2 patients. VIP scans were positive in 9 of 10 patients with carcinoid tumors and in 4 of 4 patients with insulinomas. Some tumors with positive VIP scans were also visualized with somatostatin analogues (4 of 17 colorectal adenocarcinomas, 8 of 9 carcinoids, and 2 of 2 insulinomas). In vitro binding studies confirmed the presence of VIP receptors on gastrointestinal tumors. CONCLUSIONS: Scanning with radiolabeled VIP can visualize intestinal tumors and metastases that express receptors for VIP.

Adenocarcinoma↗

PubMed1994

Cross-competition between vasoactive intestinal peptide and somatostatin for binding to tumor cell membrane receptors.

Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide with a wide range of biological activities. Recent data suggest that functional VIP receptors are expressed on various tumor cells. Somatostatin (SST) and its long-acting analogue octreotide (OCT) are potent inhibitors of tumor cell growth and secretion. In the present study, the interactions between VIP and SST/OCT on primary tumors (insulinomas, n = 3; VIPomas, n = 2; intestinal adenocarcinomas, n = 5; neuroblastomas, n = 5; papillary thyroid cancers, n = 7; carcinoids, n = 5; ductal breast cancers, n = 8; small cell lung cancers, n = 3; ACTH-producing hypophyseal adenomas, n = 5; pheochromocytomas, n = 5) as well as on tumor cell lines (A431, HT29, PANC1, COLO320, HMC1, and KU812 cells) were analyzed by use of 123I-labeled VIP and 123I-labeled Tyr-3-OCT. Cross-competition between VIP and SST/OCT for binding to tumor cells was observed. The rank-order of potency for displacement of 123I-labeled VIP binding to intact A431 cells was VIP [concentration causing half-maximal inhibition (IC50) = 2.9 +/- 1.9 (SD) nM] > OCT (IC50 = 9.3 +/- 1.7 nM) = SST > substance P = secretin (IC50 = 1 microM). Binding of 123I-labeled Tyr-3-OCT to A431 cells, in turn, was inhibited by OCT = Tyr-3-OCT (IC50 = 1.5 +/- 0.3 nM) = SST > VIP (IC50 = 4.9 +/- 1.1 nM). This rank-order of potency was also obtained for primary tumors and tumor cell lines. Furthermore, SST and OCT inhibited VIP-induced [3H]thymidine incorporation, cyclic AMP formation, and tyrosine kinase activity with IC50 values < 10 nM. Together, these data provide evidence for functional interactions between SST and VIP on various tumor cells. These interactions may involve peptide cross-competition at cellular binding sites and may have implications for the biology and pathophysiology of respective cells and disease states.

Adenosine Triphosphate↗

PubMed1994

Comparison of iodine-123 low-density lipoprotein (LDL) and indium-111 LDL binding to mononuclear cells of healthy normolipaemic controls and patients with heterozygous familial hypercholesterolaemia.

The binding of radiolabelled lipoproteins, iodine-123-labelled low-density lipoprotein (LDL) and indium-111-labelled LDL, to peripheral blood mononuclear cells (MNCs) was compared in normolipaemic subjects and in patients with heterozygous familial hypercholesterolaemia (FH). 123I-LDL and 111In-LDL binding to MNCs exhibited high-affinity, highly specific, time- and temperature-dependent binding reaching saturation at concentrations above 50 nM. The number of LDL binding sites (Bmax) was significantly (P < 0.01) lower in FH patients (P < 0.001; 123I-LDL: Bmax 279 +/- 44 ng protein/10(8) MNCs; 111In-LDL: Bmax 309 +/- 43 ng protein/10(8) MNCs) as compared with controls (123I-LDL: Bmax 2874 +/- 246 ng protein/10(8) MNCs; 111In-LDL: Bmax 3145 +/- 339 ng protein/10(8) MNCs). The corresponding dissociation constants (Kd) were 16 +/- 8 nM for 123I-LDL and 12 +/- 6 nM for 111In-LDL in healthy volunteers (123In-LDL vs 111In-LDL, P < 0.05). In FH patients, the Kd values were 20 +/- 8 nM for 123I-LDL and 16 +/- 6 nM for 111In-LDL (P < 0.05 vs controls for both 123I-LDL and 111In-LDL). 111In-LDL binding to MNCs was inhibited (IC50) by 30 +/- 8 nM in healthy controls and 38 +/- 12 nM in FH patients (P < 0.05). 123In-LDL binding to MNCs was inhibited (IC50) by 34 +/- 8 nM in healthy controls and 46 +/- 10 nM in FH patients (P < 0.05). Taken together, these results suggest a reduced number of LDL receptors expressed on MNCs from FH patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗

PubMed1994

Combined use of 123I-labelled BCD-F9 and 4C4 monoclonal antibody with dissimilar specificity for breast cancer: implication for the detection limit of immunolymphoscintigraphy in the assessment of axillary lymph node metastases.

To determine whether the detection limit of immunolymphoscintigraphy (ILS), reported to be > or = 1 cm, can be improved by comparing imaging after administration of breast cancer-specific monoclonal antibody (MAb) BCD-F9 and breast cancer-nonspecific 4C4, 25 patients with suspected breast cancer were given injections of both 123I-labelled MAbs. The ILS was performed independently for both MAbs, the 4C4 scans serving as an ipsilateral negative control, and was used preoperatively to detect lymph node metastases. Twenty-one patients had breast cancer of whom 11 patients suffered from axillary involvement. Single interpretation of BCD-F9 scans gave true positive results in six of 11 and true negative results in 12 of 14 patients, whereas combined interpretation of BCD-F9 and 4C4 scans gave true positive results in nine of 11 and true negative results in 14 of 14 patients. On the basis of comparison of scintigrams of both MAbs, ILS allowed the detection of lymph node metastases 0.3-0.8 cm in diameter (n = 3). Immunohistochemistry of BCD-F9 and 4C4 MAbs of tumour-free and tumour-bearing lymph nodes correlated with ILS, with the exception of one patient. The study suggests that comparing scans obtained with BCD-F9 and 4C4 MAbs may improve the detection limit of ILS in the preoperative staging of axillae.

Axilla↗

PubMed1993

Technetium-99m labelled LDL as a tracer for quantitative LDL scintigraphy. I. Tracer purification, in vitro and in vivo long-term stability, in vitro validation and biodistribution.

The goal of the present study was to optimize technetium-99m labelling of low-density lipoprotein (LDL) and to investigate the in vitro and in vivo properties of the tracer to determine whether its application for quantitative scintigraphy of hepatic LDL receptor activity is feasible. LDL labelled with iodine-125 by the iodine monochloride method was used as a reference tracer. Comparison of different assessments of radiochemical purity [trichloro-acetic acid precipitation (%ppTCA), paper chromatography, size-exclusion chromatography and chloroform-methanol extraction] exhibited %ppTCA to be superior as a parameter of tracer quality. In spite of a high radiochemical purity immediately after labelling, modifications of 99mTc labelling of LDL did not overcome the poor long-term stability of the tracer. Subsequent dialysis in phosphate buffer over about 3 h sufficiently increased the long-term stability in vitro and in vivo. The competitive recognition of dialysed 99mTc-LDL and 125I-LDL with native LDL by high-affinity binding sites was demonstrated in human hepatoma cells (HepG2) and human fibroblasts. Biodistribution data of simultaneously injected 99mTc-LDL and 125I-LDL in New Zealand White rabbits showed a high uptake of both tracers in tissues with high LDL receptor activity, yet 99mTc-LDL uptake exceeded 125I-LDL uptake by two- to sevenfold. In contrast to 125I-LDL, 99mTc-LDL showed a higher unspecific uptake into the bone marrow and the spleen, suggesting an additional uptake mechanism probably via the scavenger pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

SPECT imaging of dopamine and serotonin transporters with [123I]beta-CIT. Binding kinetics in the human brain.

Single photon emission computerized tomography (SPECT) studies in non-human primates have previously shown that the cocaine derivative [123I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane ([123I]beta-CIT) labels dopamine transporters in the striatum and serotonin transporters in the hypothalamus-midbrain area. Here, we report on the regional kinetic uptake of [123I]beta-CIT in the brain of 4 normal volunteers and 2 patients with Parkinson's disease. In healthy subjects striatal activity increased slowly to reach peak values at about 20 hours post injection. In the hypothalamus-midbrain area peak activities were observed at about 4 hours with a slow decrease thereafter. Low activity was observed in cortical and cerebellar areas. The striatal to cerebellar ratio was about 4 after 5 hours and 9 after 20 hours. In 2 patients with idiopathic Parkinson's disease striatal activity was markedly decreased while the activity in hypothalamus-midbrain areas was only mildly diminished. Uptake into cortical and cerebellar areas appeared to be unchanged in Parkinson's disease. Consequently, in Parkinson's disease the striatal to cerebellar ratio was decreased to values around 2.5 after 20 hours. These preliminary methodological studies suggest that [123I]beta-CIT is a useful SPECT ligand for studying dopamine and possibly also serotonin transporters in the living human brain.

Adult↗

PubMed1993

Scintigraphic evaluation of functional hepatic mass in patients with advanced breast cancer.

Recent studies suggest a high specificity of 99mTc-galactosyl neoglycoalbumin (99mTc-NGA) receptor scanning in vivo by providing both morphological and functional diagnosis of liver disease. In 22 patients with advanced breast cancer 99mTc-NGA (150 MBq; 50 nmol) was exclusively trapped by the liver, the images showing 'cold spots' in areas of liver metastases formation. A two-tailed analysis was performed: the time activity curves recorded for the liver and precordial area were subjected to a kinetic receptor-calculating model allowing an estimation of the NGA-receptor concentration of the liver (i.e. hepatic binding protein, HBP) as well as calculation of the residual functional liver volume (RFLV) via the S.P.E.C.T.-study. In breast cancer patients with liver metastases a significantly (P < 0.01) lower HBP-concentration was estimated (0.65 +/- 0.16 vs 0.82 +/- 0.17 mumol l-1) as evidenced by a lower 99mTc-NGA-accumulation in the liver resulting also in a significantly (P < 0.001) lower RFLV (739 +/- 348 vs 1336 +/- 184 ml). In four amonafide-treated patients (800 mg m-2 intravenous infusion over 3 h) approximately one week after one chemotherapy cycle a significant (P < 0.05) increase in HBP-concentration (0.56 +/- 0.10 vs 0.72 +/- 0.06 mumol l-1) of the liver was found corresponding with an increase in RVLF (546 +/- 297 vs 670 +/- 265 ml). These regulatory mechanisms at the HBP level measured in vivo provide further evidence that 99mTc-NGA should have promise as a clinically useful receptor radiopharmaceutical for both quantification of liver function and assessment of liver morphology.

Aged↗

PubMed1993

Binding of 111In-labeled LDL to platelets of normolipemic volunteers and patients with heterozygous familial hypercholesterolemia.

Low density lipoproteins (LDLs) were isolated by ultracentrifugation and radiolabeled with 111In. The in vitro binding of these radiolabels onto platelets of normolipemic volunteers (n = 15) and patients (n = 36) with heterozygous familial hypercholesterolemia (FH) was investigated. Binding was saturable and indicated high-affinity binding sites capable of binding 1,757 +/- 289 ng protein of 111In-LDL per 10(9) platelets (dissociation constant [Kd], 6 +/- 3 micrograms protein/mL) in healthy volunteers and significantly (p < 0.001) lower amounts in the FH patients (mean, 633 +/- 341 ng protein/10(9) platelets; Kd, 10 +/- 5 micrograms protein/mL). The capacity of native LDL to displace bound 111In-LDL by half amounted to 10 +/- 4 micrograms protein/mL in volunteers and 22 +/- 8 micrograms protein/mL in FH patients (p < 0.001). Treatment with gemfibrozil alone or in combination with cholestyramine in 10 patients resulted in increased 111In-LDL binding by platelets (470 +/- 307 [mean +/- SD] ng protein/10(9) platelets before therapy, 948 +/- 650 ng protein/10(9) platelets after 2 months of therapy [p < 0.01], and 1,272 +/- 701 ng protein/10(9) platelets after 6 months of therapy [p < 0.01]). Significant correlations between 111In-LDL binding capacity and apolipoprotein B (r = -0.83, p < 0.001) and LDL cholesterol (r = -0.80, p < 0.000) concentrations were found. Patients with clinically manifested atherosclerosis (p < 0.01) and those with diabetes mellitus (p < 0.05) had significantly lower platelet LDL binding sites. The findings demonstrate 111In-lipoprotein-specific binding sites on human platelets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

The role of iodine-123-Tyr-3-octreotide scintigraphy in the staging of small-cell lung cancer.

The purpose of this study is to investigate the role of 123I-Tyr-3-octreotide scintigraphy in staging small-cell lung cancer (SCLC), its efficacy for the discrimination of limited and extensive disease stages and its regional sensitivity for different metastatic locations. Twenty patients with histologically confirmed SCLC and 50 radiologically staged tumors sites were investigated by an imaging protocol including dynamic (0-30 min p.i.), static (30 min, 90 min, 4 hr, 24 hr p.i.) and SPECT (90 min p.i.) studies. The primary tumor site was visualized in 84%, whereas the best delineation was noted in early planar (15-30 min p.i.) and SPECT studies, due to a rapidly decreasing tumor-to-background ratio. Lymph node metastases were seen in 73%, but SPECT was needed for anatomical localization. All three adrenal metastases could be identified in sequential planar images. One clinically unsuspected brain metastasis was seen, whereas a second clinically overt metastasis was not visualized. The global and regional sensitivity for liver and bone metastases was unsatisfactory. In summary, 78% (7/9) of the patients with extensive disease were correctly identified by scintigraphy alone. We conclude that 123I-Tyr-3-octreotide scintigraphy is a substantial tool in the staging work-up of SCLC if it is performed initially to allow fast identification of patients with extensive disease stages and save additional radiological or invasive examinations. Yet, 123I-Tyr-3-octreotide scintigraphy cannot substitute liver sonography or conventional bone scanning in patients who have no scintigraphic evidence of distant tumor spread.

Carcinoma, Small Cell↗

PubMed1993

Dopamine D2 receptor imaging and measurement with SPECT.

Only recently it has become possible to label and visualize dopamine D2 receptors in the living human brain using an [123I]labeled ligand and the SPECT technique. Iodobenzamide (S(-)IBZM) is a substance with high affinity and high specificity for D2 receptors and was used in controls and in patients with different extrapyramidal disorders. After the i.v. administration of 5mCi (185 MBq) of [123I] labeled S(-)IBZM data collection was performed with a rotating double head scintillation camera between 60 and 110 minutes. In a semiquantitative approach a ratio was calculated between mean counts/pixel in the striatum and a region in the lateral frontal cortex, which gives an index of receptor density. In a group of 21 controls this ratio is 1.73 +/- 0.09. A highly significant age-related decline is found in controls and in 57 patients with PD. PD patients without L-DOPA or dopamine agonist treatment do not differ from controls (1.72 +/- 0.09; n = 18), whereas patients under dopaminergic therapy show a significantly lower binding ratio (1.65 +/- 0.13; n = 39; p = 0.017) suggesting receptor downregulation. Comparing the striatum ipsi- and contralateral to clinical symptoms in 18 hemiparkinsonian patients shows slightly but significantly higher values on the contralateral side, indicating receptor supersensitivity (1.71 +/- 0.11 vs. 1.66 +/- 0.09; p = 0.0014). No correlation between D2 receptor binding and clinical stage, duration of disease or duration of dopaminergic therapy exists. Markedly reduced ratios are measured in 7 patients with progressive supranuclear palsy and multiple system atrophies and in 18 patients with Huntington's disease (1.40 +/- 0.09 and 1.37 +/- 0.12 respectively; p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

[Radiosynovectomy with dysprosium-165 iron hydroxide].

Treatment of chronic rheumatoid synovitis (RS) is directed to control the inflammatory process causing pain and disability. Radiation synovectomy is suggested to be an alternative to surgical treatment, but its clinical use has been restricted because of significant leakage (> 10%) associated with the use of the standard radionuclide 90-Yttrium (used as 90-Yttrium silicate colloid) and because of its long physical half-life of 64 hours prolonging the patients' stay in the hospital. 165-Dysprosium possesses promising nuclear properties for the treatment of patients suffering from RS. The maximum soft tissue penetration of its beta-particles is 5.7 mm which is the range being necessary to penetrate the inflamed synovia. Using as carrier ferric hydroxide macroaggregates (DFH) 165-Dy is expected to minimize the cumulative radiation dose to non-target organs by its very low leakage. Animal studies were performed in 13 rats and 6 rabbits to obtain the rationale and safety data for its clinical evaluation. These studies revealed that 98.2 +/- 0.6% of the injected dose remained in the joint with a nontarget organ uptake of less than 0.1%. Clinical results were obtained from 8 patients with rheumatoid arthritis. 24 hours after injection scintigraphy was performed over the treated joint and the liver region revealing no detectable leakage of the injected activity from the joint. Blood pool activity was also assessed revealing a leakage of 0.02% of the dose injected in the knee 24 hours after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Liver function in acute viral hepatitis as determined by a hepatocyte-specific ligand: 99mTc-galactosyl-neoglycoalbumin.

Twelve patients with recently diagnosed acute viral hepatitis underwent serial 99mTc-galactosyl neoglycoalbumin scanning of the liver (for up to 8 mo). Injection of 99mTc-galactosyl neoglycoalbumin (150 mBq) at a rate of 3.5 mg (50 nmol; 1 ml) revealed that the liver is the exclusive site of tracer uptake. Simulation of 99mTc-galactosyl neoglycoalbumin kinetics allowed quantification of galactosyl neoglycoalbumin binding to human hepatic binding protein. Return of liver function test scores to normal values was associated in two patients with hepatitis A, in four patients with hepatitis B and in two patients with non-A, non-B hepatitis virus infection, with increases in hepatic binding protein concentration (up to three times the initial concentration), binding rate constant and hepatic blood flow. In the other four patients (three patients with hepatitis B and one patient with cytomegalovirus infection) a prolonged course of disease was monitored. In the mean, hepatic binding protein increased from 0.41 +/- 0.11 mumol/L after onset of acute hepatitis (n = 12) to 0.78 +/- 0.21 mumol/L after 6 mo of follow-up (n = 10) (p less than 0.001). During this period, binding rate constant (72.4 +/- 12.6 vs. 82 +/- 11.5 mumol/L/sec; p less than 0.05) and hepatic blood flow (0.027 +/- 0.0051 vs. 0.031 +/- 0.0083 L/sec; p less than 0.05) increased. Hepatic binding protein concentration correlated highly with actual laboratory test results for liver function (r = 0.98; p = 0.0001). We conclude that scintigraphic evaluation of functional liver cell mass using the new receptor-tracer 99mTc-galactosyl neoglycoalbumin could provide an in vivo diagnostic means of quantifying liver function and assessing liver morphology. In addition, our findings suggest that changes in hepatic binding protein-receptor concentration are likely to occur in vivo.

Acute Disease↗

PubMed1992

Concomitant aspirin treatment abolishes the antiatherosclerotic effects of the calcium channel blocker isradipine mediated by PGI2.

108 male rabbits, aged 6 months, with experimental hypercholesterolemia and experimental abdominal aortic lesioning received different regimen of antiatherosclerotic treatment; 36 of them were treated with isradipine, a dihydropyridine calcium antagonist (0.3 mg/kg/daily), 36 with isradipine in combination with aspirin whereas 36 animals received placebo. The entry of 125I-radiolabelled LDL into the aorta was demonstrated to be significantly diminished in isradipine-treated rabbits as well as positive Sudan-III-staining and aortic cholesterol content were in comparison to placebo. This benefit was almost completely abolished by concomitant aspirin-treatment. The notable increase in vascular prostacyclin (PGI2) is supposed to mediate the strong antiatherosclerotic effect of isradipine resulting in an inhibition of LDL-entry and vascular cholesterol accumulation. Aspirin almost totally blocked the raise in PGI2-synthesis by the inhibition of cyclooxygenase detected in isradipine-treated animals. It can be concluded, that aspirin-treatment may minimize the antiatherosclerotic actions of calcium antagonists which are mediated by the PG-system.

Animals↗

PubMed1992

In vivo quantification of cholesterol content in human carotid arteries by quantitative gamma-camera imaging after injection of autologous low density lipoproteins (LDL).

Low density lipoproteins (LDL) were isolated by immunoaffinity chromatography from 18 patients (31-70 years) suffering from primary hypercholesterolemia with angiographically proven atherosclerosis of either one or both carotid arteries. LDL were labeled with 123I (1 mCi/mg LDL) by the iodine monochloride method followed by purification with dialysis and immediately reinjected thereafter. Gamma-camera serial controls over carotid regions allowed visual detection of uptake of the radiocompound uptake in 12 out of the 18 patients. The lipid entry ratio (LER; counts over the vascular region/pixel as compared to the contralateral side after background subtraction) confirmed the visual findings. Whole body images performed until 20 h after reinjection showed 3 different kinetic types of LDL-influx into the vessel wall: decreasing (type I), increasing and then decreasing (type II) and continuously increasing (type III) with time. Four patients underwent endarterectomy within 2-7 weeks after gamma-camera imaging. Histological control revealed an extensive amount of "foam cells" in tissue samples derived during surgery and an absence of endothelial lining in samples belonging to patients with type II kinetics.

Adult↗

PubMed1992

[Lymphoscintigraphy with (123)I-marked epidermal growth factor in cervix cancer].

Several malignant neoplasms express high levels of epidermal growth factor receptors. The aim of this study was to assess whether 123I-labeled epidermal growth factor can concentrate in lymph node metastases of squamous cell carcinomas of the cervix. 14 patients with advanced cervical cancer were selected because of their high probability of lymph node metastases. Planar scintigrams were recorded from the lower and upper abdomen following subcutaneous injection of 123I-labeled epidermal growth factor into the web space of each foot. Scintigraphic images were interpreted without knowledge of computerized tomography scan (n = 13) and ultrasound (n = 9) results from the pelvic lymph nodes. In 2 patients, histological verification was performed by diagnostic biopsy of pelvic lymph nodes. Nodal involvement was confirmed by computerized tomography for 4 of the 11 positive scans and by ultrasound for 2. In 11 out of 14 patients an increased uptake of 123I-labeled epidermal growth factor could also be seen in the primary tumour. Our findings suggest that targeting of cervical cancer lymph node metastases can be achieved by in vivo binding of 123I-labeled epidermal growth factor with receptors on tumour cell surfaces.

Carcinoma, Squamous Cell↗

PubMed1992

Binding of 111In-labeled HDL to platelets from normolipemic volunteers and patients with heterozygous familial hypercholesterolemia.

High density lipoproteins (HDLs; d = 1.063 - 1.21 g/ml) were isolated by ultracentrifugation and radiolabeled with 111In. The in vitro binding onto platelets from healthy volunteers (n = 15) and patients (n = 36) with heterozygous familial hypercholesterolemia (FH) was investigated. Binding was saturable and indicated high-affinity binding sites, which bound 1,882 +/- 361 ng protein of 111In-HDL/10(9) platelets (dissociation constant [Kd] = 7 +/- 3 micrograms protein/ml) in healthy volunteers and significantly (p less than 0.01) lower amounts in the FH patients (1,012 +/- 439 ng protein of 111In-HDL/10(9) platelets [Kd = 12 +/- 4 micrograms protein/ml]; p less than 0.01). The capacity to displace one half of the bound ligand (IC50) amounted to 14 +/- 3 micrograms protein/ml in healthy volunteers and 22 +/- 9 micrograms protein/ml in FH patients (p less than 0.001). Treatment with lipid-lowering drugs (gemfibrozil, alone or in combination with cholestyramine) in 10 patients resulted in an increased HDL binding capacity: before treatment, 1,280 +/- 883; after 2 months of treatment, 2,052 +/- 873 (p less than 0.05); and after 6 months of treatment, 2,127 +/- 812 ng protein/10(9) platelets (p less than 0.01). There was a significant (p less than 0.001) correlation between 111In-HDL binding data and plasmatic lipid and lipoprotein values. Furthermore, those FH patients with the additional risk factors of smoking (p less than 0.05) and hypertension (p less than 0.01) showed significantly lower 111In-HDL binding onto platelets. The findings indicate specific 111In-HDL binding sites for human platelets, which may be decreased in patients with heterozygous FH. Upregulation of HDL binding sites during lipid-lowering medication therapy supports the hypothesis that high-affinity HDL binding is involved in hyperlipemic disorders and is possibly related to the reactivity of platelets.

Adult↗