Tritium gas

The radioactive isotopes available for use as precursors for radioactive tracer manufacturing include barium [ C]-carbonate [1882-53-7], tritium gas, p2p] phosphoric acid or pP]-phosphoric acid [15364-02-0], p S]-sulfuric acid [13770-01 -9], and sodium [ I]-iodide [24359-64-6]. It is from these chemical forms that the corresponding radioactive tracer chemicals are synthesized. [ C]-Carbon dioxide, [ C]-benzene, and [ C]-methyl iodide require vacuum-line handling in weU-ventilated fume hoods. Tritium gas, pH]-methyl iodide, sodium borotritide, and [ I]-iodine, which are the most difficult forms of these isotopes to contain, must be handled in specialized closed systems. Sodium p S]-sulfate and sodium [ I]-iodide must be handled similarly in closed systems to avoid the Uberation of volatile p S]-sulfur oxides and [ I]-iodine. Adequate shielding must be provided when handling P P]-phosphoric acid to minimize exposure to external radiation. 

The introduction of tritium into molecules is most commonly achieved by reductive methods, including catalytic reduction by tritium gas, PH2], of olefins, catalytic reductive replacement of halogen (Cl, Br, or I) by H2, and metal pH] hydride reduction of carbonyl compounds, eg, ketones (qv) and some esters, to tritium-labeled alcohols (5). The use of tritium-labeled building blocks, eg, pH] methyl iodide and pH]-acetic anhydride, is an alternative route to the preparation of high specific activity, tritium-labeled compounds. The use of these techniques for the synthesis of radiolabeled receptor ligands, ie, dmgs and dmg analogues, has been described ia detail ia the Hterature (6,7). 

Since ivermectin (= 22,23-dihydroavermectin B ) is obtained by catalytic reduction of avermectin B, the same procedure using tritium gas convenientiy affords tritiated ivermectin (22,23- [JT]-22,23-dihydroavermectin B ). The preparation of a tritiated derivative containing a 22,23-double bond starts with the readily available 5-ketone, which is reduced with [JT]-sodium borohydride stereospecificaHy to a 5- [JT]-derivative (40). Carbon-14 labeled avermectins can be obtained by a biosynthetic process using sodium (l- C)propionate as labeled precursor (48). 

Properties of T2O. Some important physical properties of T2O are Hsted in Table 2. Tritium oxide [14940-65-9] can be prepared by catalytic oxidation of T2 or by reduction of copper oxide using tritium gas. T2O, even of low (2—19% T) isotopic abundance, undergoes radiation decomposition to form HT and O2. Decomposition continues, even at 77 K, when the water is fro2en. Pure tritiated water irradiates itself at the rate of 10 MGy/d (10 rad/d). A stationary concentration of tritium peroxide, T2O2, is always present (9). AH of these factors must be taken into account in evaluating the physical constants of a particular sample of T2O. 

Mass Spectrometer. The mass spectrometer is the principal analytical tool of direct process control for the estimation of tritium. Gas samples are taken from several process points and analy2ed rapidly and continually to ensure proper operation of the system. Mass spectrometry is particularly useful in the detection of diatomic hydrogen species such as HD, HT, and DT. Mass spectrometric detection of helium-3 formed by radioactive decay of tritium is still another way to detect low levels of tritium (65). Accelerator mass spectroscopy (ams) has also been used for the detection of tritium and carbon-14 at extremely low levels. The principal appHcation of ams as of this writing has been in archeology and the geosciences, but this technique is expected to faciUtate the use of tritium in biomedical research, various clinical appHcations, and in environmental investigations (66). 

The production of tritium-labelled organic compounds was enormously facilitated by K. E. Wilz-bach s discovery in 1956 that tritium could be introduced merely by storing a compound under tritium gas for a few days or weeks the radiation induces exchange reactions between the hydrogen atoms in the compound and the tritium gas. The excess of gas is recovered for further use and the tritiated compound is purified chro-matographically. Another widely used method of... 

When specifically labelled compounds are required, direct chemical synthesis may be necessary. The standard techniques of preparative chemistry are used, suitably modified for small-scale work with radioactive materials. The starting material is tritium gas which can be obtained at greater than 98% isotopic abundance. Tritiated water can be made either by catalytic oxidation over palladium or by reduction of a metal oxide ... 

Ifi-Ditritiodihenzo- -dioxin, prepared by reductive dechlorination of 1,6-dichlorodihenzo-p-dioxin with tritium gas, is chlorinated in chloroform solution, containing catalytic amounts of iodine and ferric chloride, to produce 1,6-ditritio-2,3,7,8-tefrachlorodibenzo-p-dioxin. 

The samples of l,6-T2-DBpD and l,6-T2-2,3,7,8-Cl4-DBpD are useful in metabolism and mode of action studies. For example, when incubated with rabbit liver microsomes, l,6-T.>-DBpD is extensively metabolized to polar product(s) but only when these preparations are fortified with reduced nicotinamide-adenine dinucleotide phosphate. Under the same conditions l,6-T2-2,3,7,8-Cl4-DBpD is completely resistant to metabolic attack. In some types of studies, a higher specific activity possibly is desirable i.e., >1 Ci/mmole), and this can be achieved, with the methodology already developed, by using larger amounts of tritium gas or working on a larger synthetic scale so that it is not necessary to add unlabeled materials to assist in crystallization steps where a certain minimum amount of compound is necessary. 

Tritiated or " C-tagged hydrocarbons (including tritium gas) can be measured by using a liquid scintillation counter or a gas proportional counter [1717,1718]. 

Two di-tritiated isocarbacyclin methyl esters 116 and 117 in the title have been synthesized95 from (Z)-olefinic precursors 118 and 119 at the >-side chain by catalytic hydrogenation with tritium gas (equations 44 and 45). The therapeutic candidates for cardiovascular deseases96, 116 and 117, were required for preclinical studies and for use in RIA analysis. 

Synthesis of tritium-labelled brefeldin-A by catalytic isotope exchange with tritium gas... 

Figure 12. Fracture Appearance of Conventionally Forged Type 21-6-9 Steel after Exposure to Tritium Gas (5000 psi, 350°C) and Aged for Helium Build-In from Tritium Decay (a) 253 appm helium and (b) 627 appm helium. Arrows Indicate Direction of Crack Propagation.

As an alternative, exchange of R20 with tritium gas, R2, or tritiated water with R2, can be measnred by radioative counting. R2 is connted with a gas ionization chamber, or R20 can be measnred by solution scintillation counting. 

Deuterioammonia, 188, 190 Deuteriobor ation, 191 Deuteriobromic acid, 214 Deuteriodiborane, 191 Deuterio-Raney nickel, 215 Deuterium gas and a surface catalyst, 199 Deuterium and tritium gas, 179 3,17/8-Diacetoxyestra-3,5-diene, 486 3,20-Diacetoxypregna-3,5,20-triene, 411 (20S)-2/3,3j3-Diacetoxy-5a-pregn-7-en-6 one-20-carboxylic acid methylester, 301 Diborane, 89, 100... 

WILZBACH PROCEDURE. Exposure of organic compounds to tritium gas yields tntiated products of high activity without extensive radiation damage. Concentrations of tritium ranging from 1 to 90 millicuries per gram have been obtained with quite varied compounds. 

By Reduction of Unsaturated Precursors The method of choice for labeling with tritium is the reduction of a suitable unsaturated precursor (containing a double bond, carbonyl group, etc.) with carrier-free tritium gas or tritiated metal hydrides. The major limitation of this method is the availability of a suitable unsaturated precursor of the desired compound. It is essential to carry out the synthesis in a non-hydroxylic solvent (dioxane, ethyl acetate, etc.). Reductions carried out in alcohol or water will lead to almost complete exchange of the tritium gas with the solvent. 

Although [3H]CH3I with a high specific activity is commercially available it can also be produced on site from tritium gas. Lee and co-workers recently published two methods for the synthesis of [3H]CH3I (scheme 1) [4],... 

Tritium-labelled veratridine (35) has been prepared, with high specific activity, by condensation of veracevine with 3-bromo-4,5-dimethoxybenzoyl chloride followed by catalytic reduction with tritium gas.79... 

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