Development of 15-(p-123I-phenyl)-pentadecanoic acid for in-vivo diagnosis of the myocardium

Radioiodinated ω-phenylfatty acids were recently proposed as radiopharmaceuticals for determining myocardial metabolic alterations. Therefore uptake and elimination of different radiohalogenated phenylfatty acids were determined in blood and heart muscle of mice. The structure activity dependence i.e. the effect of length of the carbon chain, position of the substituent at the benzene ring and type of radiohalogen was studied. Highest myocardial accumulation was found in case of a phenylfatty acid with 15 carbon atoms in the alkylgroup and the radiohalogen attached to the benzene ring in the para position. No difference was observed between the radiobrominated and radioiodinated substrates. In contrast to aliphatic radioiodinated fatty acids, the radioactivity in the stomach remained almost constant (i.e. below 1% dose/organ). Thus 15-(¹²³I-phenyl)-pentadecanoic acid (IPPA) could be brought into clinical application with success. Blood clearance and urine excretion of the radioactivity were determined and the results found to agree with the expectations based on the principal metabolic path of phenylfatty acids.     

Synthesis and biological evaluation of fatty acid derivatives for myocardial imaging containing [<Superscript>99m</Superscript>Tc(CO)<Subscript>3</Subscript>]<Superscript>+</Superscript>

Radiolabeled fatty acids as myocardial metabolic agent are used for detecting ischemic heart disease, however, no ^99mTc-labeled fatty acids have potential use in clinical diagnosis. In this work, five fatty acid analogues labeled with ^99mTc were firstly synthesized and characterized, their biological behaviors were investigated. All Radiotracers had good stability when incubated in rat serum for 3 h at 37 °C. ^99mTc -CpT-12-ODPPA (8b) showed higher initial myocardial uptake (8.17% ID/g at 1 min postinjection) and good heart/blood ratio (2.58 at 30 min postinjection). ^99mTc-11-dpa-OUFA (2b) as positively charged lipophilic compounds had reasonable heart uptake (5.59% ID/g at 1 min postinjection) and good retention (1.89% ID/g at 60 min postinjection). Unfortunately, no great improvement was obtained by the five ^99mTc-labeled fatty acid analogues for the short myocardial retention and poor heart/liver ratios.     

Synthesis and evaluation of radioiodinated terminal-substituted 5-iodo-(2-thienyl) fatty acids as new myocardial imaging agents

In order to evaluate the stability of radioiodide attached to the 5 position of thiophenes substituted at the 2-position with tissue-specific groups as new radiopharmaceuticals, two [¹²⁵I]iodothienyl-substituted long-chain fatty acids have been prepared and evaluated in rats. Radioiodide was introduced into the 5 position of 17-(2-thienyi)heptadecanoic acid and 13-(2-thienyl)tridecanoic acid by K-¹²⁵I treatment of their corresponding 5-[bis-(trifluoroacetoxy)]thallium derivatives. Tissue distribution studies in rats with 17-[5-[¹²⁵I]iodo(2-thienyl)]heptadecanoic acid shows significant heart uptake and prolonged retention accompanied by in vivo deiod-ination and moderate blood levels. A comparison of the heart uptake of the 17 carbon fatty acid with a 13 carbon analogue, 13-[5-[¹³⁵I]iodo(2-thienyl)]tridecanoic acid, demonstrated a significantly greater myocardial uptake for the 17 carbon fatty acid than the 13 carbon analogue. These results suggest that the 5-iodothienyl moiety substituted at the terminal position of long chain fatty acids does not interfere with myocardial uptake and that such compounds may be of value as a new class of myocardial imaging agents.     

Kinetics of 17-(123I) iodoheptadecanoic acid in myocardium of rats

Myocardial uptake and turnover of 17-(¹²³I)-iodoheptadecanoic acid, injected i.v., was studied in rats. Kinetics of radioactivity incorporated into myocardial tissue and heart lipids as well as myocardial radioactivity recovered as¹²³I iodide were determined. Maximal heart uptake of IHA (7.9% dose/g heart) was observed as early as 30 sec., p.i., followed by mono-component elimination period. Already 10 to 30 sec p.i. 70 to 80% of total myocardial radioactivity was recovered as¹²³I iodide. IHA was incorporated only in modest amounts into myocardial phospholipids and triglycerides. Time course of total myocardial radioactivity grossly paralleled that recovered as¹²³I iodide. These findings indicate stringent limitations in utility of IHA as a tracer for assessment of β-oxidation.     

Effect of span 20 concentration on oxalic acid production from post-refining fatty acids by Aspergillus niger XP

Submerged fermentation experiments were carried out to study the stimulating effects of the surfactant Span 20 on the growth of Aspergillus niger XP mutant and oxalic acid production from the post-refining fatty acids. Span 20 concentration of 0.75 g dm⁻³ was found to be the most suitable for oxalic acid production from fatty acids. Using this dose and a fermentation medium containing 30 g dm⁻³ of post-refining fatty acids, the oxalic acid production, oxalate yield, and overall oxalate productivity were the highest. Presented at the 33rd International Conference of the Slovak Society of Chemical Engineering, Tatranské Matliare, 22–26 May 2006.     

Influence of root structure on uptake and transport of radioactive phosphorus

A simple device to observe the role of individual root zones in the uptake and transport of nutrients is described. The results confirmed the specific significance of the different anatomical structure of primary seminal maize root in ensuring the uptake and transport of phosphates. In³²p-uptake, the highest portion />40%/was taken up by zone in distance of 0–5 mm from root cap. On the other hand, the lowest transport was shown in the zone 25–30 mm from root tip. The portion of this zone was 40% from the total received supply.     

Uptake of cesium and strontium by crystalline silicotitanates from radioactive wastes

Crystalline silicotitanate inorganic ion exchanger, with a sitinakite structure is candidate material for remediation of aqueous nuclear waste streams. The syntheses of crystalline silicotitanate (CST) and Nb-substituted crystalline silcotitanate (Nb-CST) were carried out under hydrothermal conditions and the products were characterized using techniques viz., XRD, SEM/EDS, DTA/TGA, surface area respectively. Batch experiments were carried out to study the kinetics of uptake of ¹³⁷Cs and ⁹⁰Sr, to estimate the decontamination factor (DF) values and distribution coefficients (K _d) for the above synthesized CST and Nb-CST samples from actual radioactive waste solutions. The DF values for uptake of Cs and Sr by Nb-CST after 24 h of equilibration was 355 and 136 whereas for CST it was found to be 40 and 176 respectively. The K _d values for uptake of Cs and Sr for Nb-CST after 24 h of equilibration was found to be 35,490 and 13,500 mL/g respectively whereas the K _d values for uptake of Cs and Sr for CST was found to be 4,025 and 17,525 mL/g respectively. The ion exchange capacity of Nb-CST towards ⁹⁰Sr and ¹³⁷Cs was estimated to be 11.8 and 3.2 meq/g respectively whereas the ion exchange capacity of CST towards ⁹⁰Sr and ¹³⁷Cs was estimated to be 14.6 and 4.4 meq/g respectively.     

Astatine-211 labelled proteins and their stability in vivo

In an ongoing effort to obtain quantitative, rapid kit type labelling of [¹²³I] radiopharmaceuticals, we have examined organomercury precursors of [¹²³I] 15-(para-iodophenyl)-pentadecanoic acid (IPPA). Chloromercuri derivatives of phenyl pentadecanoic acid (PPA) and the PPA ethyl ester were obtained by mercuration utilizing mercuric trifluoroacetate in trifluoroacetic acid followed by treatment with acetic acid and hydrochloric acid. The most simple compound, chloromercuri PPA, proved insoluble at room temperature in the common solvents useful for radioiodination and purification. The study was extended in a systematic way to chloromercuri PPA ethyl ester and the acetoxy mercuri PPA ethyl ester. As expected, these two compounds posessed successively more useful ranges of solvent compatibility. Iodination and [¹²³I] radioiodination were carried out with the three compounds of PPA. Chloromercuri PPA was dissolved with difficulty in acetic acid at 70°C and 71% radiochemical yield of [¹²³I] IPPA was obtained during the course of a 5 minute reaction utilizing chloramine T. The chloromercuri PPA ethyl ester was dissolved in ethyl acetate/acetic acid (2/1 v/v) at room temperature and 87% radiochemical yield of [¹²³I] IPPA was obtained following 10 minutes reaction. With the acetoxy mercuri PPA ethyl ester it was possible to conduct the radioiodination in ethanol again using chloramine T. A modest radiochemical yield (r. y.) (51%) of [¹²³I] IPPA ethyl ester was obtained after 60 min. It was possible to enhance the radiochemical yield in the presence of lithium acetate (84% r. y.). The isomeric purity of the [¹²³I] IPPA ethyl ester was unexpectedly high (99.9% para) when the radioiodination was conducted at room temperature.     

A preliminary study of new imaging agents on inflammatory lesions

The purpose of the investigation was to evaluate the feasibility of imaging inflammatory lesions with five small molecular weight complexes of ^99mTc. The labeling yields of D-glucaric acid (D-Gca), citric acid (Cit), DL-malic acid (DL-Mal), L-malic acid (L-Mal) and tartaric acid (Tar) were all more than 90%. The percentage uptake/g tissue of them and ^99mTc-pertechnetate (P) in mice with turpentine-induced abscesses and abscess/muscle (A/M), blood (A/B), liver (A/L), kidney (A/K) concentration ratios were calculated. The maximum A/M ratios were 4.02±0.21 (Cit, 3h), 4.30±0.77 (D-Gca, 3h), 4.04±0.21 (DL-Mal, 6h), 3.50±0.23 (L-Mal, 1h), 3.20±0.17 (Tar, 1h) and 3.23±0.41 (P, 1h) respectively. The scintigram was obtained in a rabbit with turpentine-induced abscess after ^99mTc-D-Gca i.v. injection. Results demonstrated they all can accumulate in inflammatory lesions. Of them, ^99mTc-D-Gca is probably a potential imaging agent on inflammatory lesions.     

Radio-gas-chromatographische Kontrolle des 14C-Acetateinbaus in die Phosphatidfettsäuren der Sojabohnen

Germinating soybeans (glycine max.L.) can be employed to give a good yield of labelled phosphatides. The incorporation of ¹⁴C-acetate into fatty acids of the phosphatides, which under optimal conditions (35°C, 3000 Lux) is about 15%, was radio-gas-chromatographically controlled. It was found that exposure to light causes an increase in the formation of unsaturated fatty acids. Under the influence of a pure oxygen atmosphere at 16°C the phosphatides obtained have about 50% of the ¹⁴C-radioactivity in the oleic acid and 20% in linolic acid. This gives the preconditions necessary to obtain natural phosphatides with unequal distribution of radioactivity in the saturated and unsaturated fatty acids.

     

Synthesis of 15-(4-[11C]methylphenyl)pentadecanoic acid (MePPA) via Stille cross-coupling reaction

For experimental studies by animal PET [¹¹C]-labeled 15-(4-methylphenyl)pentadecanoic acid (MePPA) is an attractive alternative to the radioiodinated 15-(4-iodophenyl)pentadecanoic acid (IPPA) which has widely been used for imaging of fatty acid metabolism. The important physiological aspect is that the iodine atom and the methyl substituent have similar steric and lipophilic properties. For preparation of [¹¹C]MePPA, Stille cross-coupling reaction was applied since the same tin precursor as for the radiosynthesis of IPPA and readily available [¹¹C]CH₃I can be used. Unsaturated tris(dibenzylideneacetone)dipalladium(0)/tri(o-tolyl)phosphine [Pd₂(dba)₃/P(o-tolyl)₃] was taken as the catalytic system. The reaction conditions were optimized with respect to temperature, time, solvent and amount of precursor. The best radiochemical yields of 73 ± 2.8% (decay corr.) were obtained using 0.525 mg tin precursor in DMF at 80 °C already after a reaction time of 10 min. The labeled methyl ester was hydrolyzed by 1 M NaOH/EtOH at 80 °C within 3 min to give [¹¹C]IPPA in a RCY of 62 ± 3.0%. The radiochemical purity of the product assured by HPLC was >99% and the overall preparation time including HPLC purification and formulation was 40 min.     

Fatty Acid Analysis,Chemical Constituents,Biological Activity and Pesticide Residues Screening in Jordanian Propolis

Propolis is a resinous natural product collected by honeybees (Apis mellifera and others) from tree exudates that has been widely used in folk medicine. The present study was carried out to investigate the fatty acid composition, chemical constituents, antioxidant, and xanthine oxidase (XO) inhibitory activity of Jordanian propolis, collected from Al-Ghour, Jordan. The hexane extract of Jordanian propolis contained different fatty acids, which are reported for the first time by using GC-FID. The HPLC was carried out to identify important chemical constituents such as fatty acids, polyphenols and α-tocopherol. The antioxidant and xanthine oxidase inhibitory activities were also monitored. The major fatty acid identified were palmitic acid (44.6%), oleic acid (18:1∆⁹cis, 24.6%), arachidic acid (7.4%), stearic acid (5.4%), linoleic acid (18:2∆^9–12cis, 3.1%), caprylic acid (2.9%), lignoceric acid (2.6%), cis-11,14-eicosaldienoic acid (20:2∆^11–14cis, 2.4%), palmitoleic acid (1.5%), cis-11-eicosenoic acid (1.2%), α–linolenic acid (18:3∆^9–12–15cis, 1.1%), cis-13,16-docosadienoic acid (22:2∆^13–16cis, 1.0%), along with other fatty acids. The major chemical constituents identified using gradient HPLC-PDA analysis were pinocembrin (2.82%), chrysin (1.83%), luteolin-7-O-glucoside (1.23%), caffeic acid (1.12%), caffeic acid phenethyl ester (CAPE, 0.79%), apigenin (0.54%), galangin (0.46%), and luteolin (0.30%); while the minor constituents were hesperidin, quercetin, rutin, and vanillic acid. The percentage of α-tocopherol was 2.01 µg/g of the lipid fraction of propolis. Antioxidant properties of the extracts were determined via DPPH radical scavenging. The DPPH radical scavenging activities (IC₅₀) of different extracts ranged from 6.13 to 60.5 µg/mL compared to ascorbic acid (1.21 µg/mL). The xanthine oxidase inhibition (IC₅₀) ranged from 75.11 to 250.74 µg/mL compared to allopurinol (0.38 µg/mL). The results indicate that the various flavonoids, phenolic compounds, α-tocopherol, and other constituents which are present in propolis are responsible for the antioxidant and xanthine oxidation inhibition activity. To evaluate the safety studies of propolis, the pesticide residues were also monitored by LC-MS-MS 4500 Q-Trap. Trace amounts of pesticide residue (ng/mL) were detected in the samples, which are far below the permissible limit as per international guidelines.     

Decomposition of 14C containing organic molecules released from radioactive waste by gamma-radiolysis under repository conditions

Decomposition of ¹⁴C containing organic molecules into an inorganic compound has been investigated by γ-ray irradiation experiments under simulated repository conditions for radioactive waste. Lower molecular weight organic acids, alcohols, and aldehydes leached from metallic waste are reacted with OH radicals to give carbonic acid. A decomposition efficiency that expresses consumption of OH radicals by decomposition reaction of organic molecules is proposed. Decomposition efficiency increases with increasing concentration of organic molecules (1×10⁻⁶–1×10⁻³ mol dm⁻³) and is not dependent on dose rate (10–1000 Gy h⁻¹). Observed dependence indicates that decomposition efficiency is determined by reaction probability of OH radicals with organic molecules.     

Study of the uptake of inorganic ions and organic acids at theα-alumina-electrolyte interface in a colloidal system by radiochemical techniques and microelectrophoresis

The interactions of the alumina-electrolyte in the presence of inorganic ions (copper, selenium) and/or organic acids (benzoic acid, glutamic acid, phenol) have been studied. The acid-based properties of-alumina have been determined in NaCl media (pzc=8.5±0.3). Three types of hydroxy groups with different acidity constants have been found. The adsorption of copper and selenium have been described by the formation of the surface complexes: (=Al¹–OH, CuCl) and (=Al¹, SeO₃)^–. The interaction of copper with the surface oxygen atoms is strong and so is the interaction of selenium with the surface aluminium atoms, which involves a shift of the iep of alumina. For the three organic acids studied (HX), the adsorption equilibrium is:=Alⁱ–OH+HX(=Alⁱ, X)+H₂O. The interaction of the X^– group and the aluminium atoms is strong following the order: glutamic acid > benzoic acid > phenol. The uptake of selenium is uninfluenced by the presence of organic acids with carboxylic, amino-acidic and phenolic groups. The uptake of copper is highly increased by the presence of organic acids but it is not influenced by the presence of the phenolic groups. Both of these behaviours can be extrapolated to inorganic ions of the same chemical structure.     

UO 2 2+ sorption on bentonite

The capacity of bentonite and purified bentonite to remove UO ₂ ²⁺ ions from aqueous solutions has been investigated. The UO ₂ ²⁺ uptake in these clays was determined for 0.2 and 0.002M uranyl nitrate solutions. It was found that under these conditions (0.2M) the maximum UO ₂ ²⁺ uptake was 1.010±0.070 meq UO ₂ ²⁺ /g of bentonite and 0.787±0.020 meq UO ₂ ²⁺ /g of purified bentonite. In purified bentonite UO ₂ ²⁺ sorption is irreversible up to 50 hours as no desorption was observed. Such is not the case in the natural bentonite. X-ray diffraction, thermal analyses, and transmission electron microscopy were used to characterize the solids. The uranium content was determined by neutron activation analysis.     

The first total synthesis of the (±)-17-methyl-trans-4,5-methyleneoctadecanoic acid and related analogs with antileishmanial activity

The first total synthesis of the marine cyclopropane fatty acid (±)-17-methyl-trans-4,5-methyleneoctadecanoic acid was accomplished in eight steps and in 9.1% overall yield starting from 1-bromo-12-methyltridecane. The cis analog (±)-17-methyl-cis-4,5-methyleneoctadecanoic acid was also synthesized but in seven steps and in 16.4% overall yield. With the two isomeric cyclopropane fatty acids at hand it was possible to unequivocally corroborate the trans relative configuration of the naturally occurring fatty acid by gas chromatographic co-elution of the corresponding methyl esters. The cis isomer was cytotoxic to Leishmania donovani promastigotes with an IC₅₀ of 300.2 ± 4.2 μM.     

Lipid Production by Arctic Microalga Chlamydomonas sp. KNF0008 at Low Temperatures

A lipid-producing microalga, Chlamydomonas sp. KNF0008, collected from the Arctic was capable of growing at temperatures ranging from 4 to 20 °C, and the highest cell density was measured at 15 °C and 100 μmol photons m^?2 s^?1 light intensity under continuous shaking and external aeration. KNF0008 showed the elevated accumulation of lipid bodies under nitrogen-deficient conditions, rather than under nitrogen-sufficient conditions. Fatty acid production of KNF0008 was 4.2-fold (104 mg L^?1) higher than that of C. reinhardtii CC-125 at 15 °C in Bold’s Basal Medium. The dominant fatty acids were C16:0, C16:4, C18:1, and C18:3, and unsaturated fatty acids (65.69%) were higher than saturated fatty acids (13.65%) at 15 °C. These results suggested that Arctic Chlamydomonas sp. KNF0008 could possibly be utilized for production of biodiesel during periods of cold weather because of its psychrophilic characteristics.

     

Statistical Evaluation of the Quality Control Results of 99mTc(Sn)-DPD

The results of the quality control of ^99mTc-DPD produced during five consequtive years are statistically evaluated. Radiochemical purity of the kit determined in 75 batches was 98.3±1.3%. TLC on silica gel with the mixture of acetone and methanole (1:1, v/v) was used to determine the content of free pertechnetate. The labeled complex and ^99mTc-hydrolyzate was separated by using ascending paper (Schleicher & Schull) chromatography and lN NaCl as the mobile phase. Reliable results were obtained showing that the content of the impurities ^99mTc-pertechnetate and ^99mTc-hydrolyzate is 1.7±1.3% and 3.4±2.1%, respectively. The biodistribution depends on the quantity of DPD. For the animal experiments its content should be 70–80 g/kg b.w. The experiments revealed that the mean value of bone distribution was 8.8±1.9%/g and in muscles 0.043± 0.42%/g. The uptake in liver and kidneys was below 3%, i.e., 0.65±0.29 and 1.71±0.68%/organ, respectively. The bone/muscle ratio should be at least 160. The analysis shows that the obtained values are arranged around their, statistically allowed, mean values.     

Determination of the Main Fatty Acids in Sunflower-Seed Oil by a Nuclear Magnetic Relaxation Technique

A rapid procedure for determination of the main unsaturated fatty acids in sunflower-seed oil was developed on the basis of the NMR relaxation characteristics of oil triglyceride protons. The determination errors were ±2 and ±4% for oleic acid and linoleic acid, respectively (compared to the results obtained by gas–liquid chromatography).     

Determination of SCFAs in water using GC-FID. Selection of the separation system

In the present study, an analytical procedure was developed for the determination of short-chain fatty acids (SCFAs) in landfill leachate and municipal wastewater employing injection of aqueous samples to gas chromatograph with flame ionization detector (GC-FID). Chromatographic conditions such as a separation system, injection volume, oven temperature program were investigated and selected. With two columns, one with a polar (polyethylene glycol) and one with a non-polar (dimethylpolisiloxane) stationary phase, good separation of SCFAs, containing from 2 to 8 carbon atoms, was achieved. The sample volume was 2 μL and the temperature program 80 °C (30 s) then 7 °C min⁻¹ to 220 °C (2 min). LOQs values were below 0.25 mg L⁻¹. The concentrations of the acids in the landfill leachate studied ranged from 0.45 ± 0,059 (average ± extended uncertainty) mg L⁻¹ for pentanoic acid to 15.2 ± 0.73 mg L⁻¹ for ethanoic acid. Concentrations of SCFAs in the municipal wastewater were lower than LOQs.