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PubMed2001

Synthesis of high-specific-radioactivity 4- and 6-[18F]fluorometaraminol-PET tracers for the adrenergic nervous system of the heart.

Fluorine-18- (t(1/2) 109.8 min) and carbon-11 (t(1/2) 20.4 min)-labeled norepinephrine analogues have been found previously to be useful positron-emission-tomography (PET) radioligands to map adrenergic nerve terminals of the heart. Metaraminol ((1R,2S)-2-amino-1-(3-hydroxyphenyl)-1-propanol) is a metabolically stable structural analogue of norepinephrine and possesses high affinity towards the norepinephrine transporter and the vesicular monoamine transporter. This paper presents the radiosynthesis of new positron-emission-tomography halogeno analogues of metaraminol labeled with high specific radioactivity. Firstly, fluorine-18-labeled 4-fluorometaraminol (4-[18F]FMR or (1R,2S)-2-amino-1-(4-[18F]fluoro-3-hydroxyphenyl)-1-propanol) and its three other stereoisomers were prepared based on the following key steps: (a) condensation of the corresponding no-carrier-added labeled fluorobenzaldehyde with nitroethane, and (b) HPLC (C18 and chiral) resolution of the diastereomeric product mixture into the four individual enantiomers. Secondly, the corresponding 6-fluoro analogues, fluorine-18-labeled 6-fluorometaraminol (6-[18F]FMR or (1R,2S)-2-amino-1-(2-[18F]fluoro-5-hydroxyphenyl)-1-propanol) and its three other enantiomers, were prepared in an analogous way. Typically, 0.48-0.55 GBq of 4-[18F]FMR and 0.14-0.15 GBq of 6-[18F]FMR could be obtained after 120-160 min total synthesis time, with a specific radioactivity of 56-106 GBq/micromol. Furthermore, the synthesis of racemic 4-fluorometaraminol and 6-fluorometaraminol as reference compounds was performed. as well as independent chiral syntheses of the optically active (1R,2S) enantiomers. For the chiral syntheses, the key step was an electrophilic fluorination with acetyl hypofluorite of (1R,2S)-configurated organometallic derivatives of metaraminol. Tissue distribution studies in rats suggested that both 4-[18F]FMR and 6-[18F]FMR display similar affinity towards the presynaptic adrenergic nerve terminal in the heart. From a practical point of view, 4-[18F]FMR appeared to be the more attractive candidate for future PET investigations, due to higher radiochemical yields.

Animals↗
PubMed1994

Synthesis of [3',5'-3H2]-alpha-fluoromethyl-tyrosine as a radioactive specific label of rat brain tyrosine hydroxylase.

The [3',5']-ditritio-alpha-fluoromethyl-tyrosine 4 (specific activity 15.0 Ci/mmol) has been synthesized and used as a radioactive probe for rat neuronal tyrosine hydroxylase (TH). The route of synthesis for the preparation of 3 and 4 allowed us to not only introduce a fluorine atom into 3/4 using an inorganic source of fluorine (CsF), but also to take advantage of the high-yielding cyclization of (alpha,beta)-acetamido alcohols mediated by diethylaminosulfur trifluoride (DAST) to give the corresponding oxazolines. The distribution and metabolism of 4 have been studied in control conditions within the rat locus caeruleus (LC). Intracisternal injection of 20 microCi of 4 was followed by a rapid disappearance of 4 (t1/2 = 1.5 h) and by a specific accumulation of radioactivity into the LC anatomical limits. This was investigated each 140 microns along the caudo-rostral axis of the noradrenergic nucleus. In each anatomical interval, its distribution correlated nicely with already described caudo-rostral distribution of TH in noradrenergic cells. Thus, 4 may provide a reliable measure of TH activity in such catecholamine structures.

Animals↗
PubMed2000

Radioactivity measurements for the thin layer activation technique

Thin layer activation (TLA) is one of the promising techniques employing radiotracers at low levels of radioactivity for material performance studies such as wear and corrosion. The principle of TLA is the creation of an appropriate radionuclide in a given material to a well defined depth of a selected area. This activation is realised by exposure of the component to a charged particle beam using, e.g., a cyclotron facility. If the material is subjected to mechanical or chemical degradation, any loss of the activated material will result in a loss in radioactivity of the activated component. The sensitivity of TLA technique is high due to the capability of low level radioactivify measurement performed by gamma spectrometry. The sensitivity of TLA is below 0.1 microm thickness loss or 1 ng mass loss. In the present paper, some applications of TLA in ongoing research at the Institute for Health and Consumer Protection of the European Commission are presented.

Journal Article↗
PubMed2001

Automated synthesis and purification of [18F]bromofluoromethane at high specific radioactivity.

[18F]Bromofluoromethane was synthesised from dibromomethane by substitution of bromine with [18F]fluoride. The synthesis and separation of the [18F]bromofluoromethane were automated. [18F]Bromofluoromethane was used to convert a phenolic and a thiophenolic precursor into a labelled ether and thioether, respectively. The specific radioactivity of these labelled products was determined with both high-performance liquid chromatography (with UV-absorbance detection) and liquid chromatography (with mass spectrometric detection). The median for the specific radioactivity, corrected at the end of radionuclide production, was 934GBq/micromol (range 40-9900 GBq/micromol; n = 83).

Automation↗
PubMed2001

Measurement of radioactivity and radon exhalation rate in different kinds of marbles and granites.

Geological materials usually contaminated with naturally occurring radioactive materials (NORM) have become a focus of great attention. These NORM under certain conditions can reach hazardous contamination levels. Some contamination levels may be sufficiently severe that precautions must be taken. The present study deals with 60 geological samples (marble and granite) from both Egyptian and foreign locations. The studied samples were analyzed and the concentrations in Bq/kg dry weight of radioisotopes were determined by gamma-ray spectrometry using hyper-pure germanium (HPGe) detector in Bq/kg dry weight. The absorbed dose rate due to the natural radioactivity in the samples under investigation ranged from 2.45 +/- 0.07 to 64.44 +/- 1.93 nGy/h for marble and from 41.55 +/- 1.25 to 111.94 +/- 3.36 nGy/h for granite. The radium equivalent activity varied from 5.46 +/- 0.16 to 150.52 +/- 4.52 Bq/kg for marble samples and from 229.52 +/- 6.89 to 92.16 +/- 2.76 Bq/kg for granite. The representative external hazard index values for the corresponding samples are also estimated and given. The radon exhalation rates for marble and granite samples were also calculated by using solid state nuclear track detector (CR-39). The value of radium exhalation rate varied from 8.0 +/- 2.39 to 30.20 +/- 5.06 Bq/m2/d for marble and 6.89 +/- 1.72 to 25.79 +/- 4.38 Bq/m2/d for granite and the effective radium content was found to vary from 1.700 +/- 0.51 to 6.42 +/- 1.08 Bq/kg for marble and 1.29 +/- 0.32 to 5.63 +/- 0.96 Bq/kg for granite. The values of the radon exhalation rate and effective radium content are found to correspond with the values of uranium concentration measured by the HPGe detector in the corresponding sample.

Journal Article↗
PubMed2002

Radioactivity in bottled waters sold in Mexico.

Measurements of gross alpha and beta activities were made on 21 domestic and international brands of bottled (purified and mineral) water sold in the Mexican market to assess its radiological quality. Alpha and beta activities were determined using a liquid-scintillation detector with pulse-shape analysis feature. All the purified water had values of beta activity lower than the limit for potable drinking water (1.0 Bq/l), while three brands surpassed the limit of alpha activity (0.1 Bq/l). The limit for alpha radioactivity content was exceed by three mineral waters; the results show a correlation between radioactivity content and mineral salts, which are related with the origin and treatment of the waters.

Alpha Particles↗
PubMed2002

Environmental pollutant isotope measurements and natural radioactivity assessment for north Tushki area, south western desert, Egypt.

Natural radioactive materials under certain conditions can reach hazardous radiological levels. The natural radionuclide (238U, 232Th, 40K) contents of rock samples at various locations in the North Tushki area were investigated using gamma-spectrometric analysis. Estimates of the measured radionuclide content have been made for the absorbed dose rate of gamma radiation. The equivalent radium (Req) and the external hazard index (Hex) which resulted from the natural radionuclides in soil are also calculated and tabulated. The studied samples have been collected from various rock exposures in the North Tushki area. The distribution of major oxides, U and Th were studied. It is found that the enrichment and depletion of the major oxides are mainly due to the effect of hydrothermal alteration, which caused mobility of some major oxides, which increases some elements and decreases others. It is important to mention that the study area is far from the development region of the Tushki project and is only a local hazard. Therefore, additional regional studies of the Tushki Project area should be under taken to explore any unexpected environmental hazard due to the high concentration of the radioactive elements, which have been observed at its north boundary.

Journal Article↗
PubMed2003

Potential of pottery materials in manufacturing radioactive waste containers.

Various pottery materials were evaluated for possible use in manufacturing containers for radioactive waste. Their potential was examined from the viewpoints of the effectiveness of disposal and the changes induced in them by gamma rays. Samples of these materials were irradiated with high-energy neutrons and gamma rays in a reactor near its core. the physical and mechanical properties of the materials before and after gamma irradiation (in a 60Co gamma cell) were compared. The study showed that pottery materials are resistant to radiation. Therefore, they were proposed for manufacturing drums for disposal of radioactive waste of high gamma activity.

Journal Article↗
PubMed1999

Natural radioactivity of Indian building materials and by-products.

Conventional building materials and by-products from coal power plants which are being used or have the potential for use in buildings in India were analysed for natural radioactivity due to the presence of 226Ra, 232Th and 40K using gamma-ray spectroscopy. The materials examined in this work showed the radioactivity levels below the limit estimated from radium equivalent activity the criterion formula for gamma-activity suggested for acceptable radiation doses attributable to building materials in OECD countries.

Coal↗
PubMed2000

Determination of specific radioactivity for (76)Br-labeled compounds measuring the ratio between (76)Br and (79)Br using packed capillary liquid chromatography mass spectrometry.

Packed capillary liquid chromatography with electrospray mass spectrometry was used for direct determination of the specific radioactivity by calculation of isotope ratios between the (76)Br- and (79)Br-labeled analogues of N-((3-aminomethyl)benzyl)-4-bromobenzamide. Using 20 microL injections on packed capillary columns, sufficient mass sensitivity was attained for the determination on an injected amount of radioactivity corresponding to approximately 2 MBq (0.3 pmol of the (76)Br isotopic analogue).

Benzamides↗
PubMed2004

A novel electrophilic synthesis and evaluation of medium specific radioactivity (1R,2S)-4-[18F]fluorometaraminol, a tracer for the assessment of cardiac sympathetic nerve integrity with PET.

(1R,2S)-4-[18F]fluorometaraminol (4-[18F]FMR), a tracer for cardiac sympathetic innervation, was synthesized by electrophilic aromatic substitution. A trimethylstannyl precursor, protected with tert-butoxycarbonyl protecting groups, was radiofluorinated with high specific radioactivity [18F]F2. Specific radioactivity of 4-[18F]FMR, in average 11.8 +/-3.3 GBq/micromol, was improved 40-800-fold in comparison to the previous electrophilic fluorinations. The biodistribution of 4-[18F]FMR in rat was in accordance with the known distribution of sympathetic innervation. 4-[18F]FMR showed no metabolic degradation in left ventricle of rat heart, where the uptake was high, rapid and specific.

Animals↗
PubMed1999

Different brain radioactivity curves in a PET study with [11C]beta-CIT labelled in two different positions.

The cocaine congener 2beta-carbomethoxy-3beta-(4'-iodophenyl)tropane (beta-CIT) has a chemical structure that enables labelling with carbon-11 either by N-methylation or by O-methylation. The regional brain uptake of [N-methyl-11C]beta-CIT and [O-methyl-11C]beta-CIT was compared in cynomolgus monkeys using positron emission tomography (PET). The striatal uptake of radioactivity after intravenous injection of [O-methyl-11C]beta-CIT reached a plateau at 30-40 min, whereas the uptake of [N-methyl-11C]beta-CIT increased continuously during the time of the PET measurement. Two of the putative labelled metabolites, [N-methyl-11C]beta-CIT-acid and [O-methyl-11C]nor-beta-CIT were prepared and examined with PET to investigate if they may enter the brain and thus add to the radioactivity uptake obtained with [11C]beta-CIT. Less than 0.4% of injected [N-methyl-11C]beta-CIT-acid entered the brain whereas 5-6% of [O-methyl-11C]nor-beta-CIT entered the brain and accumulated in the striatum and in the thalamus. The fraction of [O-methyl-11C]nor-beta-CIT obtained in plasma after intravenous injection of [O-methyl-11C]nor-beta-CIT, however, never exceeded 3%. Consequently, the formation of [N-methyl-11C]beta-CIT-acid and [O-methyl-11C]nor-beta-CIT cannot be the explanation for the different time-activity curves in the monkey brain demonstrated with [11C]beta-CIT labelled in two different positions. An unidentified labelled lipophilic metabolite, detected in monkey plasma after injection of [O-methyl-11C]beta-CIT, remains as the only possible explanation for the differences between [N-methyl-11C]beta-CIT and [O-methyl-11C]beta-CIT.

Animals↗
PubMed1996

An alternative to radioactive microsphere for measuring regional myocardial blood flow, Part 2: Laser-Doppler perfusion monitor.

OBJECTIVE: To compare measurements of regional myocardial blood flow volume between microsphere measurement of regional flow (0.5- to 2- g tissue sampling) and a potential alternative measure, local flow (1 mm3) in the microcirculation measured by laser-Doppler perfusion monitor. DESIGN: Prospective, randomized, controlled. SETTING: University research laboratory. PARTICIPANTS: Pigs. INTERVENTIONS: After anesthetization, in 5 pigs (25 to 30 kg), the left anterior descending coronary artery was isolated and its resting flow measured by a perivascular-Doppler flowmeter. Left ventricular pressure and first time derivative of left ventricular pressure were measured. The laser-Doppler probe needle (type N) (Model ALF-21, Transonic Systems, Inc, Ithaca, NY) was inserted 2 to 3 mm into the wall of the left ventricle, parallel to the coronary artery. All 5 pigs were subjected to 0 (control), 50% , 75%, and 100% constriction of the left anterior coronary artery. MEASUREMENTS AND MAIN RESULTS: Measurements by radio-active microspheres correlated poorly with those by laser-Doppler and extremely poorly with those by perivascular Doppler flowmeter. For percent change from baseline in the constricted arterial zone, radioactive measurements correlated well with those by laser-Doppler but not those by Doppler flowmeter. Also, radioactive measurements of percent change in flow in the circumflex (nonconstricted) zone and laser-Doppler measurements in the constricted arterial zone did not correlate well. CONCLUSIONS: Laser-Doppler can be recommended for experimental research to monitor local flow. These measurements may relate to change in regional flow during normal perfusion and hypoperfusion. Before the laser-Doppler perfusion monitor can be used clinically, tissue trauma from the 0.55-mm needle needs to be evaluated.

Animals↗
PubMed2000

Equal induction and persistence of chromosome aberrations involving chromosomes 1, 4 and 10 in thyroid cancer patients treated with radioactive iodine.

A number of in vitro studies have questioned the assumption of random distribution of breaks in radiation-induced chromosome aberrations. The therapeutic application of radioactive 131I in thyroid cancer patients offers a good opportunity to study the induction and persistence of cytogenetic damage involving different chromosomes in vivo. Using whole-chromosome painting probes and triple colour painting by fluorescence in situ hybridization (FISH), we have analysed the frequency of chromosomal aberrations (CAs) involving chromosomes 1, 4 and 10 in peripheral blood lymphocytes of 10 thyroid cancer patients sampled before and 1 week, 1 year and 3.5 years after therapeutic application of radioactive iodine in a self-controlled, longitudinal study. A highly significant 3.4-fold increase in the frequency of chromosome breaks was observed 1 week after treatment with a similar representation of all chromosomes analysed. Although a significant decrease in dicentrics was observed during the first year after treatment, the frequency of chromosome aberrations remained over control levels until the last sampling time, 41-47 months post-treatment. The same behaviour, in terms of induction and persistence, was observed for all three chromosomes, confirming our previous results in vitro and rejecting the reported suggestion that chromosome 10 is radiosensitive in vivo. Our finding that the dynamics of radiation-induced CA in vivo is independent on the chromosome of choice suggests that this variable is not important in retrospective studies.

Adult↗
PubMed2002

Radioactive gold grain implants in recurrent and locally advanced head-and-neck cancers.

PURPOSE: The radioactive gold grain applicator and seeds offer the flexibility necessary for effective use in the treatment of difficult sites of head-and-neck cancers. This study reviews our experience with gold grain (198Au) implants in locally advanced head-and-neck cancer to demonstrate their efficacy and feasibility. METHODS AND MATERIALS: This study reviewed the charts of 94 patients who were treated with gold grain implants (1970-1995) and who were treated with radioactive 198Au implants. Thirty-seven of the subjects had implants located in the head-and-neck region, and these form the basis for this report. Of these, eight of the cases were located in the supraglottic larynx, five in the nasopharynx, four in the retromolar trigone, two in the oral cavity, four in the base of the tongue, four in the maxillary antrum, four in the palate, two in metastatic cervical lymph nodes (of unknown primary tumor), two in the tonsillar fossa, one in the pyriform fossa, and one in the posterior pharyngeal wall. Twenty-eight were recurrent cases after prior surgeries and radiation. Six were residual locally advanced cases, and 3 patients had their implants for a second primary tumor in an area that had been irradiated before. The gold grains were inserted with a Royal Marsden gun and 198Au, 130-180 MBq per seed. The median number of seeds implanted was 34. The total radiation dose, delivered at a margin of 0.5 cm around the target volume, ranged from 40 to 120 Gy, with a median of 80 Gy. RESULTS: Complete local control was achieved in 33% and was contingent on two factors: (1) the size of the lesion implanted and (2) the histology and possible primary tumor site. In 19 tumors with a diameter greater than 2.5 cm, only 2 (11%) had complete tumor control. Conversely, 9 of 14 patients (64%) who had lesions smaller than 2.5 cm experienced successful local control (p = 0.002). Palatal-adenoid-cystic tumors had an average progression-free survival of 52 months, compared with 13, 9, and 4 months, respectively, in nasopharyngeal, oropharyngeal, and supraglottic squamous cell carcinoma. Palliation was successfully accomplished in 76% of the cases. Cessation of bleeding occurred in 50% of the subjects, pain control was achieved in 88%, and 60% experienced relief of dysphagia. CONCLUSIONS: Gold grain implants have a role in the palliation of recurrent head-and-neck tumors, particularly for sites difficult to reach via other techniques, such as the supraglottic larynx, base of the tongue, hypopharynx, and the nasopharynx. Local control is best achieved in lesions less than 2.5 cm in dimension and is most successful in slow-growing tumors.

Aged↗
PubMed1979

Tracking radioactive larvae of Strongyloides ratti in the host.

Infective larvae of homogonic Strongyloides ratti grown in faecal culture with 32P or 75Se acquired a significant amount of radioactivity which was firmly attached to them. Heating removed most of the 32P but left 75Se in place. Subcutaneous injection of virgin and nursing mother rats with living and heat-killed radioactive larvae resulted in a pattern of labelling in the small intestine of injected animals and, in the case of 75Se, those of suckling pups, which can only be explained if labelled worms follow the natural migratory routes. The use of this tool in migratory studies is discussed, with precautions to allow for flaws in the technique.

Animals↗
PubMed1992

Rotavirus detection by dot blot hybridization assay using a non-radioactive synthetic oligodeoxynucleotide probe.

A synthetic oligodeoxynucleotide of 40 nucleotides corresponding to nucleotides 33-72 of the gene coding for the viral protein VP7 of rotavirus, was used as a nucleic acid probe to develop a non-radioactive hybridization method for rotavirus detection. The probe was labelled at the 3' end with biotin-7-dATP. The sensitivity and specificity of the dot blot hybridization assay for rotavirus detection was evaluated with 303 stool specimens. The results indicate that the hybridization assay has a higher sensitivity than both PAGE and EIA. Among the rotavirus strains tested 37 different electropherotypes were found. The results suggest that rotavirus diagnosis by dot hybridization using a non-radioactive probe may become routine laboratory procedure because it is simple, highly specific and very sensitive.

Base Sequence↗