CIATION ACHERS
CURRENT STATUS OF RADIOISOTOPE UTILIZATION' EDWIN A. WIGGIN Isotopes Division, U. S. Atomic Energy Commission, Oak Ridge, Tennessee
FOUR years ago this month the first shipment of radioactive isotopes produced in a nuclear reactor left the Oak Ridge National Laboratory to be used in a cancer research investigation a t the Barnard Free Skin and Cancer Hospital in St. Louis, Missouri. Since that time over 12,000 more shipments have gone to approximately 750 departments of some 430 institutions for hundreds of investigations in the fields of medicine, agriculture, industry, and the basic sciences. In addition, over 830 shipments have gone to about 160 institutions in 27 foreign countries for similar studies. Does this represent a large program-a real contribution of the peacetime development of atomic energy? In one sense it does. Prior to World War I1 and the advent of the nuclear reactor, the only source of man-made radioactivity was particle accelerators such as the cyclotron. Although the cyclotron remains, even today, a much more versatile radioisotope production unit, its capacity is small and its operation time-consuming. For this reason the use of radiomaterials produced at that time was primarily limited to those institutions having cyclotron facilities, or to about 75 laboratories. This means, then, that the availability of reactor-produced radioisotopes has increased the number of laboratories using them by a factor of about ten. Certainly this is on appreciable growth in the short span of a few years. On the other hand, the distribution of radioisotopes is not as expansive as it conceivably could be if we were to consider only the potential usefulness of various radioisotope applications. The reasons for this are many and varied although all the limiting factors are overshadowed by one-the lack of adequately trained scientists. However. to annreciate the over-all situation and ..
some of the problems involved one should have a pretty good idea of how radioisotopes can be used and the extent to which they have been used to date. ISOTOPES AS TRACER ATOMS
In their most generally useful role radioisotopes are employed as tracer atoms, that is, as atoms which can be used to label other atoms and molecules for the purpose of following them through complex reactions and processes. Radioisotopes as tracer atoms form the basis for the isotopic method of analysis, which derives its uniquely polverful applicability from three important factors: (1) chemical identity, (2) sensitivity, and (3) specificity. All tracer applications are based on the premise that isotopes of the same element have identical chemical properties. For example, all isotopes of carbon regardless of whether they are stable or radioactive have identical chemical characteristics. Carbon 13, which exists in nature at a concentration of only 1.1 per cent behaves just like the more abundant carbon 12 and man-made radioactive carbon 14. In a similar may, stable phosphorus 31 exhibits the same chemical properties as radioactive phosphorus 32. The sensitivity of the radioisotope technique is attributed to the fact that the presence of the radiomaterial is detected by the radiation which it emits in disintegrating. With radiation instruments such as the Geiger counter and ionization chamber it is possiblc in the case of short-lived materials such as radioactive sodium 24 to detect the presence of as little as 4 X 10-19 grams of the isotope. This sensitivity is, of course, about a million million times greater than that, ordinarily obtained by commonly used analytical methods. Even for radioactive isotopes of very long half-life such as carbon 14 (over 5000 years) where a larger number of atoms are required for detection, the ' Presented at the Twelfth Summer Conference of the New England Association of Chemistry Teachers, University of Con- sensitivity of this type of measurement is over a million times that of chemical methods. necticut, Storrs, Connecticut, August 22, 1950 632
NOVEMBER, 1950
But even more important than sensitivity is the specificity of the radioisotope technique. It arises from the fact that a specific batch of atoms (the radioactive ones) can be detected and followed independently of all other atoms which are present in the system. The number and complexity of the reactions or processes into which the labeled material may enter have no effect on the certainty of identification. For example, specific carbon positions within a complex organic compound may be labeled and then the movement of these labeled carbon atoms followed, even though they may become part of other molecular components during the reaction being studied. ANALYTICAL TECHNIQUES
There are three distinct ways in which radioisotopes may be used as analytical tools. These may be referred to as "tracer analysis," "isotope dilution analysis," and "activation analysis." Tracer analysis, as shown in Figure 1, is designed to follow the fate of a radioelement or labeled material from one stage to a later stage of a reaction or process. It. is primarily a qualitative technique and is useful when one merely wishes to determine the presence or absence of a particular substance in an agglomerate of other materials. Because of the radioactive tag or label this determination can be made quickly a t concentrations far below those permitted by other methods. Illustrative of tracer analysis is the study carried out with radiocarbon 14 on the mechanism of the Fischer-Tropsch synthesis. This is the catalytic reaction whereby mixtures of hydrogen and carbon monoxide are converted at elevated pressures and temperatures to long-chained hydrocarbons such as gasoline. The tracer studies were designed to determine if a met.al carbide of the metal catalyst is an intermediate in the synthesis. In the first phase of the study, hydrogen and carbon monoxide were reacted over an iron catalyst containing t,racerquantitiesofcarbon 14labeled iron carbide. I t was assumed that if the iron carbide were an intermediate, the initial hydrocarbons produced would contain appreciable quantities of CI4 since the first quantities of carbon entering into the reaction would tend to displace the labeled carbon in the carbide. As a further check the experiment was repeated, this time using the radiocarbon to label the carbon monoxide. Here it was reasoned that if the carbide were an intermediate, the initial hydrocarbons formed would contain little or no radiocarbon since most of the labeled carbon would be used in forming the carbide. From this study investigators were able to prove that iron carbide is not a major intermediate in the reaction. The results have since been confirmed by thermodynamic calculations. Isotope dilution analysis is a modification of tracer analysis. This method of analysis is particularly useful when the substance, the concentration of which is to be determined, cannot be quantitatively separated from other materials in the system. he technique, as shown in Figure 2, is based on introducing into the
AOD O(
0
Know"
lWlYW
1
0
U(IWI
mas
rrwrlr 1AID 1m
@
WIWY
U P I W I om~
wmm
ADVANTAGES:
-
I R A D I O C H U I W U L Y I I S N O N E S H O M AMOUNT Of
T IW LICR l l W W
sample to be analyzed an amount of radiomaterial mixed in known ratio with a stable isotope of the same element. Any change in this ratio, usually referred to as the specific activity, will be due to the dilution caused by the same element already present. This particular type of analysis is especially advantageous since only the specific activities of the isotopic materials added and later sampled for analysis need to be known. Quantitative separations are required a t no stage of the analysis although the sample analyzed must be chemically pure. One of the best illustrations of isotope dilution analysis is the extensive series of studies which have been made on the phosphate fertilizer requirements of various crops. It has been the practice in these investigations to add varying amounts of phosphate fertilizer labeled in known specific activity with radioactive phosphorus. If the specific activity of the phosphate in the harvested crop is the same as the specific activity of the phosphate in the added radioactive RADIOACTIVE ISOTOPES FOR ISOTOPE D l W l l O N W U W S
4DVANTAGES: I - S E N S I I I V I N UYI TIYES C R E A m lH*W C I M I W W L W S 2- O U A N T I ~ A ~CREYICU SEFMW I M ~ R Enor S rrcrssu*
.IMITATIONS: I-SPECIFIC AC~IVIIY
SMOW
CHANCE
m
A
r m
OF
r n wow
JOURNAL OF CHEMICAL EDUCATION
IIDUCIION
01
RADIOAC1IVI1Y
FOR YIIVATION
ANALYSIS
I
fertilizer, the investigator immediately knows that the plant derived all of its phosphorus from the fertilizer. If on the other hand the specific activity of the plant phosphorus is less than that of the added fertilizer, it is evident that part of the plant phosphorus came from the phosphorus already present in the soil. Activation analysis involves the irradiation of an unknown sample in the nuclear reactor and the subsequent identification of the radioisotopes produced (Figure 3). This type of analysis is particularly useful where the concentration of the unknown element is too low to be identified by chemical or spectroscopic methods or where standard methods of analyses are not satisfactory because of intedering contaminants. The largest single limitation to this procedure is that a nuclear reactor or other nuclear bombarding device is hecessary for irradiating the unknown sample. For this reason this particular type of isotope analysis has not been appreciably exploited to date although a cooperative exploratory program involving the Oak Ridge National Laboratory and several leading industrial research laboratories is currently under way. RADIOAClIVI FOE STUDY OF BODY'S
SULFUR
-
135
USE OF AMINO ACIDS
I-UPTAKE OF AMINO ACIDS I N V I I I O U S DRCANS 1- HOW AM110 ACIDS ENTER IN10 UODV QROCESSLS
SOURCES OF RADIATION
Although radioisotopes are primarily useful as tracer atoms-that is, as tools of analysis as described above-an increasingly large number of ways have been found for using them as uniquely applicable sources of ionizing radiation. In these instances they have been used in applications similar to those which have employed radium for many years. With the availability of nuclear-reactor-produced radioisotopes the variety and quantity of such sources has been greatly extended. For example, the investigator now has considerable choice in the type and energy of the radiation which will best suit his purposes. To date such applications have been primarily limited to interstitial and teletherapy sources in medicine and to radioactive gages and radiographic testing in industry.
EXAMPLES OF ISOTOPE UTILIZATION The number and variety of radioisotope applications made to date are much too large even to survey
I
RADIOACTIVE CAllOW FOR SNDVING lllL FAX OF
- CI4
AN INJECTED DRUG
SHOWS: I - I N NORMAL ANIMAL 90% C l 4 ELIMINATED I N 24 HOURS AS C*02
Z - ~ N ~ OOFW(14 WI~IIER IN C A N ~ E R O ~ AND S LEUKEMIC A w a u s 5-SLOWEII RATE OF WTBOUSM O f URETWANE I N NEOFUSTK NIlYUS
here. The fact that over 2000 reports and papers of such applications have alrady appeared in about 200 scientific and technical journals will verify this. Mention of a few uses will, however, demonstrate the versatility and scope of radioisotope utilization. Biology and Medicine Radioisotopes have been used to develop an entirely new technique for studying body metabolism and for studying the synthesis, transport, utilization, and breakdown of various body components. They have been used to study the fate of metabolites (Figure 4) such as proteins, vitamins, hormones, steroids, and phospholipids; the mode of action of drugs (Figure 5) such as hypnotics, antibiotics, anesthetics, bactericides, and alkaloids; and the action of injurious agents (Figure 6) such as carcinogens, viruses, bacteria, radiation, and toxicants. Approximately 47 per cent of the total number of
NOVEMBER, 1950
RADIOACTIVE
CARBON
-
CI4
FOR STUDYING CANCER PRODUCING AGENTS-CARCINOGENS
vd@
S K I N CANCER PRODUCED
, C 1 . ,-...I
-
. - .. .. . - - .......
CANCER TISSUES-ORGANS-EXCRITl
*
I - A M O U N T OF A6ENT I N CANCER AND OTHER TISSUE 2-LOCATION OF BREAKDOWN PRODUCTS OF THE AGENT 3 - M O D E OF ACTION OF CANCER PRODUCING AGENT >D."3*6
