Indian J. Pediat., 26: 414, 1959.

THE L A B O R A T O R Y AS A GUIDE IN P R O B L E M S OF PEDIATRICS

USES OF R A D I O - I S O T O P E S . I - - G E N E R A L C O N S I D E R A T I O N S *

B. S. RAU and R. P. MISRA

Calcutta

When DALTON first put forward his atomic theory in the beginning of the nineteenth century, it was an accepted fact that all matter was com- posed of components called elements. The smallest fundamental particles of each element are its atoms. The atoms of a particular element are all exactly similar and are different from atoms of all other elements; they are indivisible and unalterable. With the discovery of radioactivity in 1896 by HENRI BECQUEREL 1 and of the electron in the following year by J. J. THOMSON 5, it became evident that the atom must have a structure and even be capable of undergoing some sort of breakdown. As a result of the pioneer- ing work carried out by LOaD RUTHERFORD and his co-workers in the early part of this century, it is now known that the atom, so long regarded as the ultimate particle of matter and incapable of further sub-division, is in itself composed of three distinct types of particles called the proton, the neutron and the electron. The atoms of every element are composed of these three fundamental particles in varying proportions. Basically, an atom is described as a miniature solar system. There is a central nucleus containing most of the atomic mass and carryinga positive electric charge. This is surrounded by a planetary system of one or more electrons. Although the positively charged nucleus (radius 10 -12 cm.) comprises a very small fraction of the atomic volume (radius 10 -3 cm.) it accounts for practically all the weight of the atom. Most of the atomic volume can be said to be relatively empty, being occupied by negatively charged electrons which are many thousand times lighter than the protons or neutrons.

The proton is a small massive particle of weight 1.6 • 10 -2t gm. and has a positive electric charge of the magnitude 4.8X10 -1~ electrostatic units. The neutron has approximately the same mass as the proton but carries no electric charge. The electron is a particle of negligible mass compared with the proton or neutron, but carries a negative electric charge of the magnitude equal to that of the proton. The actual mass of the electron is 9.1 • 10 -2s gm. These figures are of little direct interest to any one but the nuclear physicist.

The different nuclei are identified by symbols such as 5311~31, 15 W2, 55 Cla7. The subscripts are the numbers of protons in the nucleus or the ato- mic number; the letters are chemical symbols; and the superscripts are the total numbers of particles in the nucleus--the mass number. The chemical properties of an element are determined by the number of electrons in the planetary system of its individual atom, i.e., by the atomic weight. From

* From the Institute of Child Health, Calcutta. Director: K. C. CHAUDHURL Received for publication on September 10j 1959.

Rau and Misra--Uyes of Radio-Isotopes 415

this it follows that all atoms present in a sample of any one element will have the same atomic number but not necessarily the same atomic weight, i.e., all the atoms will have the same number of protons, but the number of neutrons in the nucleus may differ. These atoms, differing in the number of neutrons in their nuclei, are termed isotopes of the element; they have identical chemical reactions and, forgetting for the moment the phenomenon of radioactivity, the isotopes differ only in their atomic weights.

Practically all the known elements occur normally as a mixture of two or more isotopes. I f the neutrons and protons in different numbers are arranged together to form the nuclei, most of the combinations would be unstable. They might decay by fission into two or more fragments by emis- sion of g a m m a rays, an alpha particle, a positive electron, a negative electron or by some combination of these possibilities. Such unstable nuclei are called radioactive. Radioactivity is a spontaneous and self-disruptive phenomenon exhibited by several of the heavy elements of atomic weight greater than 206 occurring in nature. The activity consists in the emission of a complex type of powerful radiation composed of three distinct types of rays known as the alpha, beta and g a m m a rays. The result of the activity is the breaking down of the element itself for good, i.e., an irreversible self-disintegration. The activity is spontaneous in the sense that it arises solely from the intrinsic natural causes unaffected by any external agency, whether physical or chemical. Modern techniques of arti- ficial transmutation of elements have been able to produce radioactivity in many other elements much lighter than those that occur in nature. This has necessitated a distinction between natural and artificial radioactivity. The atoms of radioactive elements undergo disintegration when they emit alpha and beta rays which are corpuscular in nature. These are also radio- active. The transformation goes on until an inactive or stable product is formed.

Radioactive isotopes can be detected with great sensitivity and can be used in large dilutions in biological experiments. They can also be detected i~z situ in the human body. These two advantages have led to their extensive use in medicine. One great advantage of the investigation using radioactive isotopes is that such small amounts are needed that there is little or no interference with the processes being studied. From a medical point of view, the unique feature of radio-isotopes is the emission of ionising radia- tion. Each emission has a particular energy expressed in terms of million electron volts (MEV). The different emissions have the ability to traverse distances and penetrate through matter. The term 'ionising' is applied be- cause the profound effects produced on living tissues by these radiations are related largely to ionisation. The activity of any particular radioactive isotope decays with time. A measure of this rate of decay is its half-life, which is the time interval during which the amount of radioactivity halves in Value. This may range from a fraction of a second to millions of years for different isotopes. In radioactivity, it is the number of radioactive atoms, Which disintegrate in an unit of time, that is of real importance rather than

4

416 Indian Journal of Pediatrics

the total amount of the substance expressed in weight. The unit of radio- activity is called the "curie" which is the activity of one gram of radium in which 3"7 • 101~ atoms disintegrate per second. On account of the high cost of radium and its activity the millicurie, a sub-unit--one thousandth of a curie, is used as a standard of radioactive intensity. The atoms in one microcurie (one millionth of a curie) of a biologic tracer generally weigh less than one billionth of a gram.

The use of radioactive and stable isotopes, the so-called "tagged atoms" of isotopic tracers in the study of biological problems, is of recent origin. However, as long ago as 1923, HEvEsY s showed that labels of this type can prove invaluable as tracers. A biologic tracer is any substance that can be used to follow a metabolic path-way or compartment. Following the dis- covery of deuterium by UREu 6 in 1931 and artificial radioactivity by the CURIES 2 in 1934 the scope of tracer studies increased. With the development of cyclotrons first devised by O. W. LAWRENCE ~ in 1932 many elements could be obtained in a radioactive form, and the amounts which became available for biological work were considerably increased. The next im- portant step in the production of these radio-isotopes was the result of the construction of the first uranium pile b y FER~tI and his coworkers (1942). These piles of nuclear reactors, as they are called, are capable of producing fi'om non-radioactive elements a wide range of radioactive isotopes in a variety and abundance suitable for biologic studies. Production of stable isotopes suitable for tracer investigations in biology and medicine has gradually increased during the last two decades. Isotopes of some fifty-two out of ninety-six elements have been used in medicine.

With the rapid progress in the supply of radio-isotopes and with the available techniques for their measurements, there has been a tremendous expansion of tracer investigations in biochemistry, physiology, pharma- cology and allied subjects. To the clinician, to the diagnostician, to the surgeon and to the medical profession in general the radio-isotopes have opened a new field for speculation, investigation and for a practical appli- cation of the new and formidable tool in the biologic sciences. Haematologists would like to know about the iron metabolism as determined by tile radio- iron. Internists study blood volume, circulation time, eletrolyte balance and other functions by the use of radio-chromium, radio-sodium, radio- potassium and others. In the field of cancer control the chances are great in the sense that humanity will profit much more from the knowledge gained about the growth of cancer by the use of radioactive materials as tracers, than it will from their use as therapeutic agents. All processes, physical and chemical, can be studied with radio-isotopes, not only for the purpose of advancing our basic knowledge, but also for the exploitation of this know- ledge in the direction of our survival and the prolongation of our lives.

Radiation may be detected and measured in numerous ways. Among these are activation of photographic emulsions, scintillations produced in various crystals, colouring of certain crystals, deposition of colloids, bio- logical effects, ionisation in gases and vapours including cloud chamber

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Rau and Misra-- Uses of Radio-Isotopes 417

effects and production of heat. When radiation in the form of charged particles (alpha and beta particles, protons) or photons (X- or gamma rays) interact with matter, ionisation is produced in which positively and nega- tively charged particles or ions are formed. The ionisation or production of ion pairs under proper conditions manifests itself either as an electric current or charge. Measurement of this current or charge with suitable techniques permits the quantitative or qualitative measurements of the radiation. The basic instruments used at present for the measurement of radiation in medicine are the ionisation chamber, the Gieger-Muller and the well-type scintillation counters. The details of the operation principles of these instruments are beyond the scope of this brief article. Photographic emulsions are used considerably in medical application of radioisotopes. They are used for protection purposes and in making radio-autographs. Radio-isotopes produce the same effects on photographic emulsions as do X-rays.

The effects of radiation are more difficult of precise evaluation in the case of living organisms than in other material. There will be a variation in the response and radiation between species, individuals of the species and the components of the individual. This makes it necessary to measure the radiation by physical means to standardise the measurements and then evaluate the biologic effects on the basis of these standard values.

'~EFERENGES"

I. BECQUgEL, H.--Quoted byJ. B. RAJAN, Atomic Physics. 2rid Edition. Page 278, 1953. 2. CugIE, J. and CURIE, P.--Quoted by G. FRIEDLANDER and J. W. KENNEDY. Nuclear

and radio-chemlstry. Third print. John Wiley and Sons, Inc., New York. Page 15, 1957. 3. HErEsy, G.--Quoted by E. H. QmMBV, S. FEITELBERG, and S. 51LVER. Radioactive

isotopes in clinical practice. Henry Kimpton, London, Page 7, 1958. 4. LAWRENCE, O. W.--Quoted by D. HALLmAY. Introductory nuclear physics. 2nd Edition,

Asia Publishing House, India. Page 295. 5. THOMSON, J. J.--Quoted byJ. B. RAJAS. Atomic Physics. 2nd Edition Page 19, 1953. 6. UxEv.--Quoted by E. H. QmMBY et d. Nuclear and Radiochemistry. Third print. John

Wiley and Sons, Inc, New York, 1957.