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Biomedical subjects

A M Friedman

Publications and source records attributed to A M Friedman.

At least 37 records · Page 2Linked to original sources
PubMed1987

Synthesis of [11C]SCH 23390 for dopamine D1 receptor studies.

The optimal conditions for the synthesis of 11C-labelled SCH 23390 by radio-methylation of its desmethyl precursor, SCH 24518, with [11C]iodomethane are described. Isocratic reversed phase HPLC was used for the purification of [11C]SCH 23390. The specific activity range in 30 runs was 10-235 Ci/mmol and average radiochemical yield was 72% based on [11C]iodomethane. Mean synthesis time was 40-60 min from the end of bombardment. Preliminary animal studies indicate that [11C]SCH 23390 would be useful in visualizing D1 receptors in a living brain by positron tomography.

Benzazepines↗
PubMed1986

Exogenous l-dopa alters spiroperidol binding, in vivo, in the mouse striatum.

The effect of exogenous l-dopa on the binding of tritiated spiroperidol, in vivo, in the murine striatum was investigated. The results obtained demonstrated that the binding of 3H-spiroperidol can be altered by the administration of l-dopa. This effect appears to be related to both the dose of spiroperidol and l-dopa given. Since l-dopa raised striatal dopamine levels in a dose dependent manner, these results suggest that the estimates of receptor parameters obtained using positron emission tomography and analogs of spiroperidol may be affected by the differences in endogenous dopamine concentrations among subjects.

Animals↗
PubMed1986

Radiobrominated spiroperidol for the study of dopamine D2 receptors.

Some neuropsychiatric disorders have been suggested to be related to the CNS dopaminergic system. In order to probe this neurotransmitter system, radiobrominated spiroperidol, a potent dopamine (DA) D2-receptor antagonist, was developed. This review deals with the routine synthesis of [75, 76, or 77Br]-p-bromospiroperidol (BrSP), its validation as a radiopharmaceutical directed to DA D2 receptors, and the imaging studies which have been done using this radioligand with either single photon tomography (SPECT) or positron tomography (PET). [*Br]BrSP will be compared to other D2 ligands currently available. The present state and future direction of DA receptor research, in particular, the quantitative aspects, will be discussed.

Animals↗
PubMed1986

The synthesis of non-steroidal estrogen receptor binding compounds labeled with 80mBr.

Estrogen receptor (ER) binding radiopharmaceuticals have potential for use in the diagnosis and treatment of cancers of the female reproductive system. Two triphenylethylene derivatives based on the structure of hydroxytamoxifen 4, a high ER binding metabolite of tamoxifen 5, have been prepared: 1-(4-dimethylaminoethoxy)phenyl]-1-(4-hydroxy)phenyl-2-bromo-2-phenyl ethylene 2 and 1,1-bis (p-hydroxyphenyl)-2-bromo-2-phenylethylene 3. Both 2 and 3 bind strongly to the ER. Compound 3 has been labeled in modest yield by direct bromination with 80mBr, which was produced by the 83Kr (d,n alpha) reaction. Radiolabeled 22, a dimethoxy precursor of 3, has been prepared in yields ranging between 40 and 60% by a bromination destannylation reaction.

Animals↗
PubMed1986

Bismuth-212-labeled anti-Tac monoclonal antibody: alpha-particle-emitting radionuclides as modalities for radioimmunotherapy.

Anti-Tac, a monoclonal antibody directed to the human interleukin 2 (IL-2) receptor, has been successfully conjugated to the alpha-particle-emitting radionuclide bismuth-212 by use of a bifunctional ligand, the isobutylcarboxycarbonic anhydride of diethylenetriaminepentaacetic acid. The physical properties of 212Bi are appropriate for radioimmunotherapy in that it has a short half-life, deposits its high energy over a short distance, and can be obtained in large quantities from a radium generator. Antibody specific activities of 1-40 microCi/microgram (1 Ci = 37 GBq) were achieved. Specificity of the 212Bi-labeled anti-Tac was demonstrated for the IL-2 receptor-positive adult T-cell leukemia line HUT-102B2 by protein synthesis inhibition and clonogenic assays. Activity levels of 0.5 microCi or the equivalent of 12 rad/ml of alpha radiation targeted by anti-Tac eliminated greater than 98% the proliferative capabilities of HUT-102B2 cells with more modest effects on IL-2 receptor-negative cell lines. Specific cytotoxicity was blocked by excess unlabeled anti-Tac but not by human IgG. In addition, an irrelevant control monoclonal antibody of the same isotype labeled with 212Bi was unable to target alpha radiation to cell lines. Therefore, 212Bi-labeled anti-Tac is a potentially effective and specific immunocytotoxic reagent for the elimination of IL-2 receptor-positive cells. These experiments thus provide the scientific basis for use of alpha-particle-emitting radionuclides in immunotherapy.

Antibodies, Monoclonal↗
PubMed1986

Deuterioglucose: alteration of biodistribution by an isotope effect.

Carbon-14 glucose, in which all carbon-hydrogen bonds were replaced by carbon-deuterium bonds (deuterioglucose), was extracted from algae growing in heavy water and exposed to [14C]carbon dioxide. The identity of [14C]deuterioglucose was confirmed by comparison with authentic material on two high performance liquid chromatography and two thin layer chromatography systems. Fermentation to lactate followed by oxidative decarboxylation demonstrated that 35% of the 14C was on carbons 3 and 4 for deuterioglucose isolated from a 24-hr algal incubation, and 61% for a 20-min incubation. Mice were injected intravenously with either (24-hr) deuterioglucose or with 14C-labeled (protio)glucose labeled uniformly. The deuterioglucose cleared more slowly from the blood, while heart and brain accumulated label more slowly. Tissue concentrations peaked at later times for deuterioglucose. Deuteration may be a useful feature of radiopharmaceutical design.

Animals↗
PubMed1985

Biological effects of background radiation: mutagenicity of 40K.

The naturally occurring radioactive isotope 40K is the single largest contributor to the internal background radiation dose in living organisms. We examined cell growth and mutation rate or frequency in several strains of Escherichia coli in (i) media containing the natural content of 40K, (ii) media containing potassium from which essentially all of the 40K had been removed by isotope separation, and (iii) media highly enriched in 40K. Growth rates (doubling times) were identical in the present or absence of 40K. In more than 40 chemostat experiments, we were unable to detect any significant differences in mutation rate to bacteriophage T5 resistance or in mutation frequency to valine resistance or tryptophan prototrophy attributable to 40K. We conclude that, in the bacterial systems we have studied, 40K does not make a significant contribution to spontaneous mutation.

Dose-Response Relationship, Radiation↗
PubMed1984

In vivo binding of spiroperidol and bromospiroperidol at low drug loadings.

The binding of spiroperidol and bromospiroperidol, in vivo, was studied over a wide range of drug dosages. It was found that while spiroperidol and bromospiroperidol bind selectively in vivo to tissues known to be high in dopamine receptor binding sites, this specificity of binding does not persist at very low doses. Such anomalous binding behavior can have implications for the non-invasive imaging of these drugs.

Animals↗
PubMed1984

Measurements in vivo of parameters of the dopamine system.

An in vivo study of the binding of the neuroleptic drugs spiroperidol and bromospiroperidol has indicated a large amount of specific binding to the dopamine-rich caudate nuclei of the murine brain. We have tested the applicability of the simple thermodynamic equilibrium equation to describe this binding and find that it seems to be a reasonable description of the process. It appears that a period of several hours is needed for reaching equilibrium, but after that time the behavior appears slowly to follow the equilibrium isotherm. One consequence of this model is the apparent competition of endogenous dopamine for the binding sites in vivo. The data can only be fitted by the calculations when the endogenous dopamine is included as a competitive ligand. This competition presents the interesting possibility of measuring the synaptic dopamine concentration by its effect on the binding of neuroleptic drugs. A second observation in these studies was the increase of nonspecific binding of bromospiroperidol at very low drug loadings. This increase is attributed to the presence of binding sites that are ubiquitously dispersed and very dilute but of high affinity.

Animals↗
PubMed1983

Properties of liposomes containing 212Pb.

The reverse phase evaporation method was used to prepare lipid bilayer membrane vesicles containing 212Pb and other markers of high specific activity. Electron microscopy and microfiltration were used to measure the sizes of the liposomes. Isotopes were released from the liposomes during exposure to serum and this leakage was prevented by complexing of small molecules with proteins or by precipitating particulate complexes within the liposomes. The in vivo distribution of 212Pb liposomes differed from the distribution of free 212Pb in that the reticuloendothelial system cleared the liposomes. Liposomes with surface dinitrophenol hapten were highly immunogenic and the humoral response to dinitrophenol was nonspecifically suppressed by 212Pb liposomes.

Animals↗
PubMed1982

Construction of a broad host range cosmid cloning vector and its use in the genetic analysis of Rhizobium mutants.

We have constructed a cosmid derivative of the low copy-number broad host-range cloning vector pRK290 (Ditta et al., 1980) by inserting a 1.6-kb Bg/II fragment containing lambda cos into the unique Bg/II site in pRK290. The new vector, pLAFR1, is 21.6 kb long, confers tetracycline resistance, contains a unique EcoRI site, and can be mobilized into and stably replicates within many Gram-negative hosts. We constructed a clone bank of Rhizobium meliloti DNA in pLAFR1 using a partial EcoRI digest. The mean insert size was 23.1 kb. When the clone bank was mated (en masse) from Escherichia coli to various R. meliloti auxotrophic mutants, tetracycline-resistant (Tcr) transconjugants were obtained at frequencies ranging from 0.1 to 0.8, and among these, prototrophic colonies were obtained at frequencies ranging from 0.001 to 0.007. pLAFR1 cosmids were mobilized from R. meliloti prototrophic colonies into E. coli and then reintroduced into R. meliloti auxotrophs. In most cases, 100% of these latter Tcr transconjugants were prototrophic.

Bacteriophage lambda↗
PubMed1982

Dynamic imaging of the respiratory cycle with 81mKr.

To define the regional ventilation of the human lung, subjects were monitored with a gamma camera, while breathing air labeled with radioactive 81mKr which is being continuously eluted from a generator. The information observed is displayed as a reiterated multiframe moving picture. This is accomplished by storing the information from multiple breaths, selecting acceptable cycles (determined by the duration of inspiration and expiration and the amplitude to extremes of the cycles), and normalizing the usable information and converting the summed data into sequential frames, which are repeatedly shown on a video screen from computer memory.

Computers↗