Administration of Radioactive Substances

In the development of most new active substances, it is required to investigate the disposition of the compound and its metabolite(s) and their rates and routes of elimination. This is generally carried out with radiolabelled compound, usually In the United Kingdom, approval of the Administration of Radioactive Substances Advisory Committee (ARSAC) is required for administration of radiolabelled compound to man. The purpose of the submission is to demonstrate that the dose of absorbed radiation is minimised by administration of the lowest dose that is consistent with meeting the objectives of the study. In general, the estimated absorbed radiation dose should be less than 500 xSv, but higher amoimts are permissible if they can be justified. The estimate is based on tissue distribution of radioactivity in animals and the pharmacokinetics in animals and man. 

In this special case, additional approval is needed from the national authorities overseeing radiation safety. For example, in the United Kingdom this is the Administration of Radioactive Substances Advisory Committee (ARSAC). Application to ARSAC only requires a summary of the study protocol, but a careful scientific justification of the amount of radiation employed and the number of subjects exposed. The EU Directive 97/43/EurATOM sets dose limits for healthy subjects and patients. 

Critical features of metabolism frequently require administration of radiolabelled material to man during ED. Such studies generally involve administration of single doses, with subsequent collection of excreta as well as blood sampling until virtually all drug has been eliminated. The clinical phase of such studies is generally not complex, but preparation for the study, with synthesis of the radioactive molecule and development of cold assays of metabolites as well as parent molecule, may take many months. Such studies also require submission of applications with detailed dosage and radioactive exposure calculations for authorisation by external bodies such as the Administration of Radioactive Substances Advisory Committee (ARSAC) in the UK. 

MBq (13.5 mCi) maximum recommended activity (Administration of Radioactive Substances Advisory Committee 1993)... 

Administration of Radioactive Substances Advisory Committee (1993) Investigations -adult patients. In Notes for guidance on the administration of radioactive substances to persons for purposes of diagnosis, treatment or research. Appendix 1, Part A. Administration of Radioactive Substances Advisory Committee - ARSAC, Oxon, UK, p 25... 

The medical man is primarily interested in the therapeutic administration of radioactive substances. Development of the technic is uneven, the furthest being in treatment with radioactive phosphorus prepared by the bombardment of red phosphorus with high speed deuterons. It is too early to judge, but artificial radioactivity is at least as good as x-ray treatment of certain blood diseases, though neither is a cure (90). 

Syao-Shan Y. 1970a. The behavior of thorium dioxide in rats after intratracheal and intraperitoneal administration. In Lefavet, Kurlyandskaya, eds. The toxicology of radioactive substances, Vol. 4. New York, Pergamon Press, 30-41. 

Indeed, these polyenoic acids are metabolized rapidly, linoleic, linolenic, and the isomers as well. The low value in one of the linoleic acid experiments must be related to a delayed resorption 74% of the activity was still present in the intestine at the end of the experiment. Only after 5 hours following administration of the substance did the expired CO2 become radioactive, whereas in all other experiments this occurred after 1 hour. It is remarkable that animals on a normal diet oxidize these substances at a faster rate than those on a fat-free diet, supplemented with the corresponding inactive acid over a period of 3-4 weeks. 

In this book the term burden means the (1) financial costs, (2) administrative, research and other resource conunitments, and (3) radiological, social and other inqncts which sod must provide or endure in connection with disposal of radioactive wastes. Burden does not have the meaning formerly used in radiation protection terminology and thus is not limited to the quantity of radioactive substances carried within a human body or organ. 

After oral and intravenous administration of radioactive labelled chlorendic acid to rats, the substance is rapidly distributed through-... 

Studies with [l- 4C]dichloroacetonitrile in rats and mice and 2- C dichloroaccto-nitrile in rats indicated that the substance is rapidly absorbed after oral administration in water. Excretion of radioactivity following dosing with l- C dichloroacctonitrilc is more rapid in mice than in rats. In mice, approximately 84% of the dose was excreted in 24 h (67% in urine, 11% in faeces, 5% as CO ), compared with 67% in rats in six days (44% in urine, 17% in faeces, 6% as CO,). Excretion of 2- < dichloroacctonitrilc radioactivity in rats accounted for about 84% of the dose within 48 h (38% in urine, 12% in faeces, 34% as CO2). The quantitative differences in the route of excretion of the two labels in rats indicate that dichloroacetonitrile is being cleaved in vivo. The 1- relabelled compound behaved like cyanide (lARC, 1991). 

The administration of radiopharmaceuticals remains the same as that outlined earlier and as illustrated in the 1978 Medicine Act (radioactive substances) amendment. 

When a radioactive substance is taken into the body by ingestion or inhalation in sufficient amounts to be a hazard, the procedure is to attempt to remove it as fast as possible so that it does not have time to become incorporated into tissues that have relatively long biological lifetimes, such as the bones. Administration of chemical complexing agents, which form stable complexes with the radioactive substances, provides a mechanism for the removal of radioactivity from the body. 

These principles are observed under production conditions during all kinds of operations at all plants and installations for reprocessing radioactive substances (Medbioextrem Federal Administration services for sanitary-hygienic supervision radiation monitoring). 

Department of the Environment, Radioactive Substances Act I960, A guide to the administration of the Act, HMSO, London (1982)... 

The remainder of the Act deals with administrative amendments to the Radioactive Substances Act, the Nature Conservancy Council and other miscellaneous waste controls. 

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