400 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS tagged compounds. In many instances quantities of radioisotopes too small to be measured by chemical means can be readily detected by special electronic devices. 3. The presence of radioisotopes can be detected in situ in intact living organisms and tissues by means of special methods without the need for biopsy, sampling or extraction. 4. Radioisotopes make it possible to study such dynamic processes as the rate of chemical transfer, exchange of components across cellular membranes and intermediate metabolism such as synthesis and breakdown of organic complexes. 5. The site of localization of radioisotopes emitting alpha and beta rays can be demonstrated by autoradiography. In order to be used for experimental purposes, a radioactive tracer sub- stance must have the following properties: 1. Be of sufficient initial concentration to withstand dilution. 2. Be sufficiently stable chemically. 3. Not interfere with the normal series of biologic and/or pathologic events in which one is interested. 4. Have an adequate radioactive half-life. 5. Not be stored in any human organ or tissue in a concentration that might prove damaging. In undertaking any tracer study it is first necessary to label, with a radioactive tag, the particular chemical or compound to be traced. But this involves more than loosely attaching a tag as one might tie a stringed label to a suitcase for identification purposes. This radioactive tag must be an integral part of the chemical. If the substance being investigated is an inorganic element or its salt, the element itself should be radioactive if an organic compound the radioactive element should be a part of the central structure. If it is a side chain that bears the radioactive tag there is a greater chance of loosing it. Of course, giving a substance a radioactive label can present numerous difficulties, and may at times be one of the limitations to the use of radio- active isotopes for tracer purposes. In some instances, compounds can be synthesized in the laboratory where the radioactive atoms can be selected and introduced by chemical synthesis at any desired position in the chemi- cal structure. In other instances the tagging may be accomplished through biosynthesis by feeding a particular radioactive atom to a living system which in turn produces the desired radioactive molecule. Once the radioactively tagged chemical or compound has been prepared it is ready to be incorporated in a selected vehicle to be used for various studies. Since the radioactive form of the substance will behave both chemically and biochemically in an identical fashion as the non-radioactive form, only small amounts of the radioactively tagged substance need be

USES AND LIMITATIONS OF RADIOACTIVE ISOTOPES 401 diluted with the non-radioactive tbrm in order to carry out tracer experi- ments. Of course, the amount that must be added will depend on the nature and purpose of the experiment and the particular radioactive iso- tope being used. With the incorporation of the radioactive substance in, let us say, an ointment base, it occurred to me that the radioactive properties of the tag could be put to its first practical use--that of demonstrating even disper- sion of the substance through the ointment base. This, of course, could be done simply enough by taking an aliquot of the mixed ointment and meas- uring its radioactivity. Knowing the total weight of the ointment and the total radioactivity of the substance added, simple calculation should tell if even distribution has taken place. Furthermore, this method should be an easy means of telling how soon after the start of the mixing process the dispersion of a particular substance in a base is complete. One might even use autoradiography to visualize the distribution of a tagged compound through an ointment or any other vehicle. (But perhaps I am complicating existing simpler methods which are being used in the industry and with which I am not familiar.) In addition to the methods now being used by pharmaceutical chemists to test for diffusion of active ingredients from a particular base (e.g., leeching of soluble dyes, colorimetric tests) it appears to me that here again radioactively tagged ingredients could be used to advantage. It should not be diflScult to measure the amounts of radioactive ingredients leaving an ointment which has been applied to a given surface. With the proper set-up, not only the amount could be measured, but also the rate and distribution of the diffusion. And of course, similar methods could be applied in various ways to test for stability, correctness of packaging and compatibility of the tagged ingredient with other added ingredients. I refer to those instances in which the changes that take place are not dis- cernible to the naked eye nor detectable by ordinary chemical means. Here the radioactive tag should be capable of demonstrating minor shifts and accumulations of the substances being studied which otherwise might go unobserved within the ointment. Whereas, the amount of radioac- tivity of the tagged ingredient could be measured in aliquots of the oint- ment taken from various parts of its container the newer needle-type Geiger probes should serve to advantage in doing measurements of radio- activity in situ. These probes could be inserted into the ointment at any point thus permitting direct measurement of the radioactively tagged ingredient without disturbing the packaging in any other way. There must certainly be many other applications for radioisotopes in the laboratory, but it is time I say something about the clinical applications of our selected ointment containing the radioactive ingredient. As for most bio-assays, the laboratory animal is usually the first to be