Chemical synthesis with tritium

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 ... 

Radiolabelled compounds are prepared by introducing artificially produced (nuclear reactor, cyclotron) radioisotopes into the molecules. This can be accomplished by chemical synthesis, biosynthesis and by special procedures (e.g. isotopic exchange, reduction of an unsaturated precursor with tritium gas). As a rule the choice of the preparation method greatly affects the principal characteristics of the radioactive product such as specific activity, type of labelling and purity... 

The combination of microbial excision of a structural fragment and subsequent re-incorporation of its labeled analog by chemical synthesis is an elegant and straightforward approach to the preparation of labeled compounds. As recently communicated, SSR126768 (S was demethylated by incubation with Mortierella isabellina MMP108 to obtain the required SSRl 136660 1571. Remethylation under standard conditions demonstrated that 5Z was a precursor suitable for carbon-11 (and therefore probably tritium or carbon-14) labeling . 

This assay is normally carried out only if positive effects have been obtained in earlier in vitro tests. The UDS test measures the DNA repair synthesis which occurs after excision and removal of a stretch of DNA containing the region of damage, induced in hepatocytes of animals treated with the test chemicals. UDS is measured by the uptake of radioactively labelled nucleotide, usually tritium-labelled th)unidine, into the DNA of the damaged hepatocytes. Animals, usually male rats, are treated with the test chemical, and... 

Bile acid synthesis can also be measured isotopically. Of these procedures Lindstedt s method is widely used because it permits the measurement of the pool size, turnover and synthesis rates of the two primary bile acids separately provided that the two differently labeled bile acids are administered and that the H-label is tightly bound and is not subjected to losses due to tritium exchange. The method may not be valid in gross bile acid malabsorption due to incomplete mixing of the labels within the bile acid pool. Comparison of the quantitative data obtained with this and GLC methods have given similar and even markedly different results (cf. 7). Usually the values of the isotopic procedure are somewhat higher than those of the GLC method, a discrepancy which has no explanation at the moment even when the nonspecific losses of tritium is taken into consideration. Hypertriglyceridemic subjects in particular produce much more bile acids on the basis of the isotopic than chemical balance. 

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