Search PubMed⌕ Search

Biomedical subjects

H Sinn

Publications and source records attributed to H Sinn.

At least 55 records · Page 3Linked to original sources
PubMed1990

Design of compounds having an enhanced tumour uptake, using serum albumin as a carrier. Part I.

The search for a radioiodinated "cumulative" protein label, stored within cells following intracellular protein degradation, suggested that plasma protein turnover of tumours might be of use. While earlier investigators were primarily interested in metabolism and utilization of plasma proteins by tumours, we tried to utilize the tumour protein turnover to channel radioiodine labelled compounds, covalently bound to serum albumin, into neoplastic tissues. To identify those parameters which influence the tumour uptake and storage, we investigated a series of compounds having different chemical and physicochemical properties. Unbound, small molecular weight compounds were rapidly eliminated from the circulatory system. They had a prolonged biological half life if linked to serum albumin (SA), especially when derivatized with deoxysorbitol. Parallel with the prolongation of the biological half-life we noted a remarkable increase in tumour uptake, which was not accompanied by increased liver activity. Furthermore, without thyroid blockade, we failed to detect significant radioiodine uptake in this organ after 24 or 72 h. This is due to the particular coupling mechanism, which may be relevant for other (radio)iodinated pharmaceuticals used in medicine. Glucose and aromatic amines, as well as aromatic aldehydes and glucamine react to form deoxysorbitol derivates, which then have similar biokinetics after linkage to serum albumin. This indicates that a new approach in tumour detection and possibly in tumour therapy may be possible when SA is used as a carrier molecule, using the described labelling procedure.

Animals↗
PubMed1990

Synthesis of positively charged phthalocyanines and their activity in the photodynamic therapy of cancer cells.

Positively charged zinc containing or metal free phthalocyanines 6a-c and 7a-c were prepared via a three step procedure starting from 4-nitrophthalonitrile. The phthalocyanines contain alkyl chains of different length in order to influence the hydrophilic vs lipophilic character of the compounds. The partition between a hydrophilic (water) and lipophilic (octanol-1) phase was determined, and the photoredox activities were investigated. Initial results on the photodynamic activity of these compounds were compared with those of Dougherty's Photofrin II on different malignant and non-malignant cell lines (XP 29MAmal, CX1, HeLa, S180 and NO17). Positively charged phthalocyanines in vitro showed a higher photodynamic activity than Photofrin II.

Animals↗
PubMed1989

Stability in biological fluids and clearance of immunoliposomes.

The in vivo and in vitro stability of liposomes having covalently bound monoclonal antibodies (MAB) connected to their surface via a disulfide bridge (about 6 anti-melanoma MAB-molecules per liposome) in tissue fluids was investigated. These immunoliposomes were composed of equimolar amounts of hydrogenated soybean lecithin and cholesterol and had a mean diameter of 113 nm. The protein-lipid binding, change of vesicle size and the release of encapsulated carboxyfluorescein (CF) were estimated. After i.v. injection into mice, an initial protein cleavage of 21% occurred within 30 min p.a., followed by a slow elimination of intact MAB-liposomes from blood circulation (t50 = 2.2 h). These liposomes had a similar elimination rate as protein-free liposomes. The in vitro results after incubation of MAB-liposomes in blood, plasma, serum and tissue fluid were very similar with regard to the protein-lipid cleavage, but the time dependence was different. The CF-release in vitro was slower (about 1.5%/d) than the protein cleavage; the vesicle size of MAB-liposomes increased substantially in contrast to protein-free liposomes in serum during 4 days.

Animals↗
PubMed1988

Evidence in liver for a disulphide-linked scavenger receptor containing a binding site for acetylated low-density lipoprotein and maleylated bovine serum albumin.

Membranes from rat liver were analysed under reducing conditions. The components of the soluble membranes responsible for the binding of acetylated low density lipoprotein (acetyl-LDL) and maleylated bovine serum albumin (Mal-BSA) were chromatographed on a polyethyleneimine-cellulose column and subsequently separated by gel electrophoresis. For both ligands a major binding protein (Mr = 35,000) was revealed by ligand blotting. A minor protein (Mr greater than 67,000) exhibited little binding. The Scatchard plot of the 131I-Mal-BSA binding data of the 35 kDa protein was linear, with a Kd of 17.3 nM. High concentrations of acetyl-LDL competed for half of the 131I-Mal-BSA binding. Excessive Mal-BSA competed for all the visible acetyl-LDL binding. The findings indicate the existence, in the reduced hepatic membrane, of a 35 kDa protein that has two binding sites for 131I-Mal-BSA and one binding site for acetyl-LDL.

Albumins↗
PubMed1987

Binding of acetylated low density lipoprotein and maleylated bovine serum albumin to the rat liver: one or two receptors?

The liver is the major organ involved in clearance of acetylated low density lipoprotein (acetyl-LDL) and maleylated serum albumin (Mal-BSA). Quantitative analysis of the hepatic uptake by sequential scintigraphy in rats shows that the hepatic uptake capacity for Mal-BSA is at least 15 times larger than for acetyl-LDL particles. A membrane-associated M approximately 250,000 daltons hepatic receptor for acetyl-LDL and Mal-BSA was 1450-fold purified from total membrane by Triton X-114 solubilization, chromatography on polyethylenimine cellulose and gel filtration. This receptor incorporated into liposomes displayed a saturable binding of [131I]Mal-BSA with a dissociation constant Kd = 15 nM and to [131I]acetyl-LDL with a dissociation constant Kd = 0.9 nM. The binding of both ligands was sensitive to poly(vinyl sulfate). The purified scavenger receptor system has a binding capacity for [131I]Mal-BSA 20 times larger than for [131I]acetyl-LDL. This is similar to the maximal removal capacity of the rat liver for both ligands in vivo. Binding studies with Mal-BSA, acetyl-LDL and anti-idiotypic receptor antibodies as competitors for [131I]Mal-BSA and [131I]acetyl-LDL binding demonstrate that [131I]Mal-BSA and [131I]acetyl-LDL compete for a common binding site. However, not all of the Mal-BSA binding sites are capable of interacting with acetyl-LDL.

Albumins↗
PubMed1986

123I-N-isopropyl-amphetamine single photon emission computed tomography as a brain imaging technique in dementia.

Because of its binding to specific cerebral amine receptor sites 123I-N-isopropyl-amphetamine (IMP) tracer activity can be used as a measure for the regional cerebral blood flow (rCBF) in the human brain. In 21 psychiatric in-patients an IMP perfusion study was performed using a rotating gamma camera system. The findings at single photon emission computed tomography (SPECT) were compared with different clinical parameters including conventional transmission computed tomography. In SPECT, two different patterns of decrease in IMP uptake could be identified. In patients with a history of cerebrovascular disease SPECT showed asymmetrical, multifocal microcirculatory defects without preference for either hemisphere. In patients with suggested Alzheimer type dementia the perfusion deficits involved the gray and white matter of the parieto-occipital lobes in a bilaterally symmetrical mode with variable extension. Thus, by using IMP-SPECT, it was possible to define the underlying pathologic condition in dementia.

Adult↗
PubMed1985

Visualization of the hepatic low-density lipoprotein receptor in rats by sequential scintiscans.

The usefulness of a gamma camera system for external imaging of the degradation sites of low-density lipoprotein (LDL) is demonstrated in rats. [131I]LDL was injected intravenously in normal rats and rats pretreated with 17 alpha-ethinyl estradiol for LDL receptor induction. Distribution of the radioligand was followed for 20 min, for perfusion control [131I]albumin was administered. Rats pretreated with 17 alpha-ethinyl estradiol showed a marked increase in the LDL uptake by the liver, which was not competed by the preinjection of physiological amounts of unlabelled LDL. It is concluded that the injection of small amounts of [131I]LDL is sufficient to image the hepatic LDL receptor and that the endogenous LDL does not compete effectively at physiological LDL levels.

Animals↗
PubMed1985

Characterization of binding sites for acetylated low density lipoprotein in the rat liver in vivo and in vitro.

Acetylated low density lipoprotein (acetyl-LDL) binding to hepatic membrane proteins of rats was analysed in vitro by ligand blotting. Specific binding could be demonstrated to two hepatic proteins with an apparent mol. wt. of 250 kd and 220 kd. Polyanionic competitors and maleylated bovine serum albumin inhibited the binding of acetyl-LDL effectively. To determine the sites of the catabolism of acetyl-LDL, [131I]-acetyl-LDL was injected intravenously into control rats and rats pre-treated with the known competitors of the acetyl-LDL binding. Distribution of the radiolabelled acetyl-LDL was followed by a scintillation camera. Six minutes after injection, the radioactivity was concentrated in the liver. The competitors and unlabelled acetyl-LDL but not native LDL reduced the hepatic uptake of [131I]acetyl-LDL dramatically. Thus, the sensitivity of the 220- and 250-kd membrane binding sites to the competitors for the acetyl-LDL binding resembled that of the hepatic compartment in vivo. Finally, an application of scintigraphy with radiolabelled low density lipoproteins for diagnostic evaluation of tumor compartments is presented.

Animals↗
PubMed1985

11C-butanol for imaging of the blood-flow distribution in tumor-bearing animals.

1-11C-n-Butanol produced semiautomatically using a cyclotron was employed to investigate the whole-body distribution and kinetics of the label of this compound. Following the administration of 11C-butanol into the aorta of two dogs, more than 80% of the activity was cleared from the blood within 1 min. The activity distribution mirrored the cardiac output distribution as determined using 121I microspheres. Within 25 min p.i., a significant release of decay-corrected activity was only observed for the liver, spleen, and kidneys. Muscle and whole-body activity showed constant levels during this period. In 45 tumor transplants from rats, the dynamic behavior of the label was studied. The tissue retention of activity following injection into the a. femoralis was approximately 100% during the 1st 15 s for both tumor and muscle (n = 6). The activity release by tumors during the 1st 10 min after intra-aortic injection was 18% +/- 4.5% (n = 39; decay corrected). In five different tumor lines (n = 10), the initial 11C-butanol uptake was related to that of muscle, and the results were correlated with the tumor-to-muscle retention of 121I-microspheres (r = 0.89). In 17 tumors, the correlation between 11C-butanol uptake and the washout rate of 133Xe resulted in a correlation coefficient of 0.96. Tumor-to-muscle uptake ratios could be equally determined using intra-aortic and intravenous injection, as evaluated by intraindividual comparison in 12 rats (y = 0.01 + 0.98x; r = 0.98). 11C-Butanol appears to be an appropriate radiotracer for the assessment of blood supply to malignant tumors relative to muscle.

1-Butanol↗
PubMed1984

N-13 L-glutamate uptake in malignancy: its relationship to blood flow.

Studies on glutamate uptake, with special reference to perfusion, were carried out in 35 rats, each bearing one of five different tumor transplants; also in 15 rats after bone fracture, and in three rabbits. Single-pass extraction of N-13 glutamate was 85-93% in the VX2 tumor of the rabbit and in muscle. Bone fracture in rats caused a threefold increase of tracer uptake 2 days after the event. In tumor transplants, the tumor-to-muscle uptake ratio reached a maximum immediately following injection of the tracer. Comparing N-13 glutamate uptake with the retention of 1-121 microspheres, identical tumor-to-muscle ratios were found for three out of five tumor lines. Comparing the uptake with that of C-11 butanol (ten rats), a close correlation was observed throughout the range of tumor lines. The results suggested that glutamate uptake by malignant tumors is related to blood flow. In nine patients with malignant or benign lesions tumor-to-muscle uptake of N-13 glutamate and TI-201 showed a linear correlation close to identity.

Adolescent↗
PubMed1980

[Pre and intraoperative volume determination of craniopharyngioma cysts (author's transl)].

Exact cystic volume measurement is a prerequisite to proper 90Y dosage in the therapy of of intracavitary monocystic craniopharyngiomas. The method of intraoperative volume measurement by a radionuclide dilution technique is compared to results obtained by preoperative volumetry using computer tomography. Both methods gave congruous results. It is pointed out that gamma camera scintigrams are essential for the early detection of complications.

Adolescent↗
PubMed1979

[Clinical relevance of 111In-bleomycine in intrathoracal neoplasms (author's transl)].

With a medium storage ratio of 1:1.4 between sound and neoplastic lung tissue additional diagnostic information cannot be obtained by positive tumor scintigraphy with 111In-bleomycine. This may be accounted for on the one hand by the diffuse borders of the storage foci, on the other hand by the relatively high storage of radioactivity in normal lung tissue.

Aged↗