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Biomedical subjects

R Albert

Publications and source records attributed to R Albert.

At least 55 records · Page 3Linked to original sources
PubMed1994

[111In]-DTPA-labeled analogues of alpha-melanocyte-stimulating hormone for melanoma targeting: receptor binding in vitro and in vivo.

Six alpha-MSH(4-10) [Nle-Asp-His-D-Phe-Arg-Trp-Lys-amide] derivatives carrying 2 or 1 or no 2,3-dihydroxy-(2S)-propyl (DHP) groups on the Lys10 amino side chain were coupled to diethylene-triaminopentaacetic acid (DTPA, a chelator for 111In) in monomeric and dimeric forms and tested for their binding activity and bioactivity in vitro with mouse and human melanoma cell lines and by receptor autoradiography to tumor sections, as well as in vivo with normal and melanoma-bearing mice: DTPA-[Nle4,Asp5,D-Phe7,Lys(bis-DHP)10]-alpha-MSH(4-10),DTPA-[Nle4, Asp5, D-Phe7,Lys(mono-DHP)10]-alpha-MSH(4-10), DTPA[Nle4,Asp5,D-Phe7,Lys10]-alpha-MSH(4-10), DTPA-bis-([Nle4,Asp5,D-Phe7,Lys(bis-DHP)10]-alpha-MSH(4-10)), DTPA-bis[([Nle4,Asp5,D-Phe7,Lys(mono-DHP)10]-alpha-MSH(4-10)) and DTPA-bis-([Nle4,Asp5,D-Phe7,Lys10]-alpha-MSH(4-10)). In the receptor-binding assays with B16-F1 mouse and D10 human melanoma cells, the KD values ranged between 0.76 and 31.17 nM and in the melanin bioassay the results were similar (EC50 values between 0.15 and 4.40 nM). The tissue distribution of the 111In-labeled compounds in C57Bl/6J mice showed that the dimeric [111In]-DTPA-bis([Nle4,Asp5,D-Phe7,Lys10]-alpha-MSH(4-10)) and the monomeric [111In]-DTPA-[Nle4,Asp5,D-Phe7,Lys(bis-DHP)10]-alpha-MSH(4-10) exhibited the lowest non-specific binding. In mice carrying B16-F1 melanoma tumors, the monomeric compound displayed 2-fold higher 111In uptake by the tumor and a much lower non-specific uptake by the liver (12-fold) and the kidneys (2.5-fold) than the dimeric derivative. This demonstrates that modification of the Lys10 side chain by DHP is a promising lead for new MSH radiopharmaceuticals for melanoma targeting.

Amino Acid Sequence↗
PubMed1994

Synthesis, radiochemistry and biological evaluation of a new somatostatin analogue (SDZ 219-387) labelled with technetium-99m.

A new derivative of octreotide SDZ 219-387 [PnAO-(D)Phe(1)-octreotide] was synthesized, which binds specifically and with high affinity to somatostatin receptors in vitro (pKi = 9.79 +/- 0.16). This new somatostatin analogue chelates technetium-99m under mild labelling conditions in good yields. The resulting [99mTc]SDZ 219-387 was stable up to 6 h after labelling and could be isolated in a pure radiochemical and chemical form by high-performance liquid chromatographic purification. The intravenous administration of purified [99mTc]SDZ 219-387 revealed that the radioligand was rapidly cleared from circulation, and tumour uptake of 0.38% ID/g was observed at 1.5 h post injection. [99mTc]SDZ 219-387 specifically interacted with somatostatin binding sites on the tumour. However, the radioligand is highly lipophilic and excreted mainly through the hepatobiliary system. As a consequence, [99mTc]SDZ 219-387 exhibits increased background activity and therefore is not appropriate for the in vivo visualization of somatostatin receptor-positive tumours and/or their metastases in the abdomen.

Animals↗
PubMed1994

Evaluation of different image acquisition techniques for a computer vision system in the diagnosis of malignant melanoma.

BACKGROUND: Digital image analysis was found to be a useful technique for improved accuracy of preoperative diagnosis of melanocytic lesions. In previous studies digitized color slides were used as input for digital image analysis. New technologies and smaller video cameras made it possible to develop a camera system that allows the digitization of skin lesions directly from the patient. OBJECTIVE: We investigated whether conventional color slides or directly digitized images should be used for a reliable recognition of malignant melanoma. METHODS: Computer features describing characteristics of the lesions were computed for 404 digitized color slides and for 309 directly acquired lesions. Statistical analysis and classifier construction was performed by the commercial statistical classification program CART. RESULTS: With the data set derived either from the color slides or from the directly digitized lesions a sensitivity of about 90% for the recognition of malignant melanoma could be obtained. CONCLUSION: Both image acquisition techniques allow a reliable detection of malignant melanoma and both are appropriate as input for an image analysis system regarding its efficiency as a diagnostic tool. However, none of the classifiers can be applied with reasonable significance to both techniques.

Diagnosis, Computer-Assisted↗
PubMed1994

IgG monoclonal antibodies that inhibit osteoinductivity of human bone matrix-derived proteins (hBMP/NCP).

Monoclonal hBMP/NCP (human bone morphogenetic protein and associated noncollagenous proteins) antibodies of the IgG class were produced. In vitro, 12 of 19 hBMP/NCP antibodies showed functional inhibition of hBMP/NCP-induced chondroneogenesis in a neonatal muscle tissue assay. Inducing factors were characterized by their inhibiting antibodies with immunoblotting. Several peptide factors seem to be involved in the cascade of induced chondro- and osteogenesis.

Animals↗
PubMed1994

Biological characterisation of [67Ga] or [68Ga] labelled DFO-octreotide (SDZ 216-927) for PET studies of somatostatin receptor positive tumors.

Radiolabelled analogues of Somatostatin (SRIF) were demonstrated to be useful for conventional gamma-camera imaging of SRIF receptor-positive tumors and their metastases. To evaluate the feasibility of positron emission tomography (PET) or SRIF receptor-positive tumors deferoxamine (DFO) was conjugated to octreotide via a succinyl linker to form a stable conjugate with the gallium isotopes 67Ga and 68Ga. This new octreotide analog, SDZ 216-927, binds specifically and with high affinity to SRIF receptors in vitro (pKi = 8.94 +/- 0.06) and exhibits SRIF like biological properties as demonstrated by the inhibition of growth hormone (GH) release from cultured pituitary cells. SDZ 216-927 was efficiently labelled with 67Ga without affecting high affinity binding to SRIF receptors. Biodistribution studies revealed that [67Ga]SDZ 216-927 was stable in vivo and rapidly cleared from the circulation, as indicated by the low amount of 67Ga detected in the blood four hours post injection (p.i.). SRIF receptor-positive tumors were clearly visualized 10 minutes p.i. in tumor bearing rats. The specificity of ligand binding in vivo was demonstrated i) by the high tumor/non-tumor ratio 4 hours p.i. (tumor/blood 22.3:1, tumor/muscle 64.5:1, tumor/liver 4.0:1, tumor/spleen 16.8:1) and ii) by a significantly lower uptake of radioactivity in the tumor after pretreatment of tumor bearing animals with an excess of unlabelled SDZ 216-927. SDZ 216-927, when labelled with the positron emitting isotope 68Ga, clearly imaged SRIF receptor-positive tumors using positron emission tomography (PET). Therefore quantitative SRIF receptor imaging with PET seems to be possible using this new radiopharmaceutical.

Animals↗
PubMed1994

Gallium-67/gallium-68-[DFO]-octreotide--a potential radiopharmaceutical for PET imaging of somatostatin receptor-positive tumors: synthesis and radiolabeling in vitro and preliminary in vivo studies.

UNLABELLED: When labeled with gamma-emitting radionuclides, somatostatin analogs have the potential to localize somatostatin receptor-positive tumors using gamma camera scintigraphy. We present a somatostatin analog, [DFO]-octreotide (SDZ 216-927), that comprises desferrioxamine B coupled to octreotide via a succinyl linker. This conjugate can be labeled with either 67Ga for gamma scintigraphy or 68Ga for PET imaging. The 67Ga-labeled conjugate is stable in vitro to autoradiolysis over a 24-hr period. METHODS: Rats bearing a somatostatin receptor-positive pancreatic islet cell tumor were injected with 20 MBq of 67Ga[DFO]-octreotide (33 GBq 67Ga/mumole). RESULTS: After 1 hr, the accumulation of 67Ga[DFO]-octreotide was 0.38 +/- 0.08 %ID/g and the tumor-to-nontumor ratios for blood, muscle, liver and intestine were 2.5, 7.4, 1.9 and 1.6, respectively. PET studies with 68Ga[DFO]-octreotide recorded a very rapid accumulation at the tumor and a subsequent residence half-life of about 6 hr. CONCLUSION: Gallium-68-[DFO]-octreotide can be used in PET studies to diagnose receptor-positive tumors such as gastroenteropancreatic, small-cell lung and breast tumors.

Animals↗
PubMed1993

SDZ CO 611: a highly potent glycated analog of somatostatin with improved oral activity.

To obtain orally active octreotide (Sandostatin, SMS 201-995) analogs a new class of glycated somatostatin derivatives were synthesized by the Amadori reaction (Maillard reaction). The synthesis, chemical and biological characterization of a series of new compounds is described. These oligopeptides bind with high affinity to somatostatin receptors and retain full biological activity. Whereas generally polypeptide hormones are almost completely inactive after oral administration, we report here for the first time that these analogs show remarkably high activity by the oral route. Thus for example SDZ CO 611, the D(+)-maltose Amadori derivative of octreotide, has about 10 times higher oral effect bioavailability than octreotide while maintaining the selectivity, metabolic stability and long duration of action of the parent compound.

Administration, Oral↗
PubMed1993

[A comparison of the two anticholinergic agents atropine and glycopyrrolate during antagonism of a muscle relaxation with pyridostigmine].

Central, peripheral and cardiac side-effects of both anticholinergic drugs atropine and glycopyrrolate were compared during the antagonism of muscle relaxation with pyridostigmine. In a randomized, double-blind fashion 50 patients were given 10 micrograms/kg of atropine and 50 were given 5 micrograms/kg of glycopyrrolate with 125 micrograms/kg pyridostigmine intravenously. Continuous Holter ECG-monitoring over 3 hours was performed. The procedure was divided into the following phases: control (5 minutes before application of antagonists), phase I (application of antagonists and the following 5 minutes), phase II (subsequent 30 minutes), phase III (until 3 hours had passed). The first 32 minutes were subdivided into periods of 4 minutes. Analysed were: 1st: The number of patients with supraventricular, junctional and ventricular beats, 2nd: The mean heart rate per period, 3rd: The incidence of central-anticholinergic syndromes and the peripheral antimuscarinic side-effects. Supraventricular beats were found after atropine in 42 patients and after glycopyrrolate in 18 patients (p < 0.001). The differences mainly occurred during phase I (atropine 15 vs. glycopyrrolate 4 p < 0.05) and III (atropine 38 vs. glycopyrrolate 18, p < 0.01). Junctional beats were found after both drugs (atropine 7 vs. glycopyrrolate 10), above all during phase III. Ventricular beats were observed after atropine (21) and glycopyrrolate (18). Atropine as well as glycopyrrolate caused an increased heart rate within the first 4 minutes (atropine 47% vs. glycopyrrolate 27%, p < 0.01). During phase III after atropine, the heart rate decreased below the control value (p < 0.05). None of the patients showed central anticholinergic syndromes after either drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

New octreotide derivatives for in vivo targeting of somatostatin receptor-positive tumors for single photon emission computed tomography (SPECT) and positron emission tomography (PET).

Two new modifications of the somatostatin analog octreotide, designed to hold the gallium isotopes 67Ga and 68Ga (DFO-SMS, Fig. 1a) and 99mTc (PnAO-SMS, Fig. 1b) have been synthesized and evaluated in vitro and in vivo in tumor bearing rats. DFO-SMS can be labeled with 67Ga3+ and 68Ga3+ with high specific activity within less than 30 minutes in a "cold kit" type formulation. The labeled conjugate is stable under physiological conditions. Moreover the binding affinity to somatostatin receptors on rat brain cortex membranes was shown to be retained. In vivo fast tumor localization was demonstrated and the pharmacokinetics proved to be favourable as the main excretion route was via the kidneys. First PET studies with [68Ga]-DFO-SMS showed a rapid accumulation in the tumor and a residence half-life at the tumor site of about 6 hours. PnAO-SMS can be labeled with 99mTc with high radiochemical purity. In vivo the radiotracer accumulates well in the tumor but due to its high lipophilicity, its main excretion route is via the hepatobiliary system.

Adenoma, Islet Cell↗
PubMed1993

OctreoScan 111 for imaging of a somatostatin receptor-positive islet cell tumor in rat.

Somatostatin (SRIF) receptors are present in a variety of human tumors such as pituitary and endocrine pancreatic tumors, brain tumors, small cell lung cancers and malignant breast tumors. The 111In-labeled SRIF analog SDZ 215-811 (OctreoScan 111) binds with a high affinity to somatostatin receptors and exhibits SRIF-like biological properties, as demonstrated by the inhibition of growth hormone release from pituitary cells. We report here the in vitro characterization of SDZ 215-811 and the in vivo imaging of an islet cell tumor grown in rats using [111In]SDZ 215-811. In vitro autoradiographies revealed a high density of SRIF receptors on the pancreatic tumor tissue. As early as 5 min after intravenous injection of [111In]SDZ 215-811 into tumor-bearing rats, the tumors were clearly localized by gamma-camera scintigraphy. Even 24 h post injection, the islet cell tumor was still detectable. The radioligand was mainly cleared from the circulation via the kidneys, with a rapid alpha-phase (t1/2 = 5.6 min) and a slow elimination phase (t1/2 = 7.3 h). Biodistribution studies revealed a relatively high accumulation of radioactivity in the kidneys, but low uptake into the liver and the intestine. High uptake of [111In]SDZ 215-811 was observed for the tumor tissue (0.92 +/- 0.07% ID/g; 1 h post injection). Interestingly, a tumor load of 0.14 +/- 0.01% ID/g was still measured after 24 h. The tumor/blood ratio was 4.93 after 24 h, indicating specific accumulation of radioactivity in the islet cell tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Islet Cell↗
PubMed1993

Classification of melanocytic lesions with color and texture analysis using digital image processing.

The incidence of malignant melanoma, the most dangerous skin cancer, has increased rapidly during the last decade, and the figures are still rising. Since well-trained and experienced dermatologists are able to reach only a diagnostic accuracy of about 75% in visual preoperative classification, the discriminating ability of digital image analysis was evaluated in more than 350 malignant melanoma and benign melanocytic lesions that had all been confirmed histologically. Color slides of melanocytic lesions were scanned and digitized. Computer algorithms were programmed in FORTRAN on a DECstation 5000/200. A feature set was calculated describing the texture, color and their distributions as well as asymmetry, size and border of each lesion. These features, together with the histologic diagnosis, were the input in a commercial statistical classification program. In contrast to the accuracy of 75% achievable by the human eye, a correct classification rate of about 92% was reached with the mathematical classifier as compared with the histologic diagnosis.

Algorithms↗
PubMed1992

Three-dimensional image processing for morphometric analysis of epithelium sections.

The reproducible classification of poorly differentiated abnormal epithelium specimens is still a diagnostic problem. The computer-aided method described here improves the differentiation between benign and malignant epithelium specimens. Hematoxylin and eosin-stained sections of normal squamous epithelium, dysplasia, carcinoma in situ, and carcinoma were scanned in a TV microscope system and analyzed by means of image processing methods on a DEC 5000/200 workstation. From the 15-20 microns thick histological sections, 3-5 focus positions in steps of 1-4 microns were scanned. The segmentation of the cell nuclei was performed automatically by color analysis and geometric operations. For each nucleus the best focus level was selected and at this level the center of the cell was calculated. Graph theoretical methods were applied to analyze the morphometry of the epithelium specimens. The minimal spanning tree was computed in the three-dimensional (3D) space of the sections with the selected centers of the nuclei as vertices. The best feature found for discrimination of the specimens is the average length of all edges in a tree. In the two-dimensional (2D) analysis we had to accept an error probability of about 20% in differentiation of dysplasia and carcinoma. In contrast to this we differentiated normal squamous epithelium, dysplasia, and carcinoma with a correct classification rate of 100% in the 3D analysis.

Carcinoma↗
PubMed1991

Intestinal absorption of the octapeptide SMS 201-995 visualized by fluorescence derivatization.

The absorption of an intact oligopeptide was investigated in rat and dog small intestine using the metabolically stable somatostatin analogue SMS 201-995. The synthetic octapeptide was coupled to 4-nitrobenzo-2-oxa-1,3-diazol to have a fluorescent label for the direct visualization. The 4-nitrobenzo-2-oxa-1,3-diazol-labeled peptide was active in displacing the corresponding hormone 125I-Tyr3-SMS 201-995 (Sandostatin; Sandoz Pharmaceuticals, Basel, Switzerland) from its high-affinity binding site in rat cortex membranes with an IC50 = 4.6 x 10(-10) mol/L. The release of growth hormone from cultured anterior pituitary cells was inhibited by the fluorescent somatostatin analogue with the same potency as by somatostatin 14 (IC50 = 6 x 10(-10) mol/L). Incubation with mucosal scrapings followed by high-performance thin-layer chromatography analysis showed that the peptide was stable against proteolysis. 4-Nitrobenzo-2-oxa-1,3-diazol SMS 201-995 was well absorbed from enterocytes of rat small intestine. The absorption was highest into jejunal cells and it could be inhibited by an excess of unlabeled peptide. A significantly lower absorption was detected in crypts compared with villus tips. No fluorescence could be seen in intestinal mucin and goblet cells. After oral administration, the 4-nitrobenzo-2-oxa-1,3-diazol-labeled peptide rapidly appeared in the blood of rats and dogs, reaching a bioavailability of 4.3% and maintaining pharmacological activity. This suggests that enterocytes are able to absorb intact oligopeptides being stabilized against proteolytic degradation through a transcellular mechanism.

Animals↗
PubMed1991

[111In-DTPA-D-Phe1]-octreotide, a potential radiopharmaceutical for imaging of somatostatin receptor-positive tumors: synthesis, radiolabeling and in vitro validation.

Somatostatin receptor-positive human tumors can be detected using radioiodinated analogues of somatostatin, both in vitro and in vivo. [123I-Tyr3]-octreotide has been successfully used in the visualization of somatostatin receptor-positive tumors by gamma camera scintigraphy, but this radiopharmaceutical has some major drawbacks, which can be overcome with other radionuclides such as 111In. As starting material for a potentially convenient radiopharmaceutical, a diethylenetriaminopentaacetic acid (DTPA) conjugated derivative of octreotide (SMS 201-995) was prepared. This peptide, [DTPA-D-Phe1]-octreotide (SDZ 215-811) binds more than 95% of added 111In in an easy, single-step labeling procedure without necessity of further purification. The specific somatostatin-like biologic effect of these analogues was proven by the inhibition of growth hormone secretion by cultured rat pituitary cells in a dose-dependent fashion by octreotide, [DTPA-D-Phe1]-octreotide and non-radioactive [115In-DTPA-D-Phe1]-octreotide. The binding of [111In-DTPA-D-Phe1]-octreotide to rat brain cortex membranes proved to be displaced similarly by natural somatostatin as well as by octreotide, suggesting specific binding of [111In-DTPA-D-Phe1]-octreotide to somatostatin receptors. The binding of the indium-labeled compound showed a somewhat lower affinity when compared with the iodinated [Tyr3]-octreotide, but indium-labeled [DTPA-D-Phe1]-octreotide still binds with nanomolar affinity. In conjunction with in vivo studies, these results suggest that [111In-DTPA-D-Phe1]-octreotide is a promising radiopharmaceutical for scintigraphic imaging of somatostatin receptor-positive tumors.

Amino Acid Sequence↗
PubMed1990

[Centroblast morphology: a morphometric evaluation by means of computer-aided image analysis].

In cytologic preparations, cell images from 30 cases of high grade malignant Non-Hodgkin's lymphoma (NHL) and 10 cases of tonsillitis have been analysed using a colour TV microscope system, high resolution scanning and image processing. Multivariate analysis of 30 cell features allowed satisfying recognition and discrimination of centrocytes, centrocyte-like centroblasts, ordinary centroblasts and multilobated centroblasts. In addition, according to their image analytical data, the ordinary centroblasts from NHL formed 5, and those from tonsillitis 4 well defined, homogeneous clusters. Even at simultaneous analysis, there was an essential overlap only between centroblast subtype 3 from NHL and subtype 9 from tonsillitis, but reliable discrimination of all the rest.

Computers↗