Palladium 103 has been obtained by reactor bombardment of palladium metal. Unfortunately, only low specific activity material containing radiation impurities such as neutron-activated iridium is obtained by this method.10 The precursor palladium 102 has a natural abundance of only 1 per cent. The material can be produced carrier-free in curie quantities by proton bombardment of rhodium, as has been demonstrated with the Oak Ridge National Laboratory 86 inch cyclotron.

Iodine is an excellent example of an element having a wide variety of useful radioisotopes. Of the 20 known radioisotopes, iodine 131 has become most familiar. The advantages of the shorter lived iodine 132 and 133 for certain purposes have already been mentioned. Considerable interest is being shown in iodine 125, a low energy photon emitter, which was overlooked for many years as a potentially valuable medical isotope. 13,22

Iodine 125 has a number of advantages in comparison with the commonly used iodine 131. The low energy of the 27.3 kev. x rays enhances detector efficiency and contrast, making possible a more accurate scanning technique. At the same time the absence of beta radiation permits comparable studies with only a few per cent of the dose received by the patient if iodine 131 were used. The 60 day half life provides long shelf life and permits long term metabolic studies.

Radiography with low-energy gamma emitters has advanced in practicality with the availability of such isotopes as iodine 125, palladium 103, promethium 147, samarium 145, gadolinium 153, ytterbium 169, and thulium 170 (Table VIII). Highly portable radiography units using various isotopes have demonstrated their capability to produce radiograms of diagnostic quality in locations where x-ray machines are impractical or impossible to use, in operating rooms, homes, disaster areas and remote locations. Besides the advantages of

power requirements, such gamma radiography units can be readily sterilized.o

NEW METHODS OF ISOTOPE LABELING

Diagnostic and research applications of radioisotopes require that numerous complex organic compounds be labeled in various positions with radioactive isotopes. The preparation and distribution of labeled compounds and radiopharmaceuticals have for many years been a commerical business. There are dozens of companies bringing out new labeled compounds. The ability to prepare useful radiomaterials often depends on starting with elemental radioisotopes having high specific activities, as produced through Commission development and production activities.

Tritium-labeled materials, while little used except in research, have possibilities for both diagnosis and therapy. The short range beta particles localize radiation effects in regions as small as cell nuclei.

One of the most valuable and commonly used labeling techniques is the Wilzbach self-labeling method, in which organic compounds are simply exposed to large quantities of gaseous tritium.15,21,23 Modifications include subjecting the system to a silent electrical discharge." While self-labeling has supplied a large number of tritiumlabeled compounds, the Wilzbach method has certain 'disadvantages. Radiolysis produces a mixture of labeled organic com

pounds which requires difficult and timeconsuming separation. The desired labeled compound represents only a small fraction of the initial radioactivity. Furthermore, multicurie quantities of gaseous tritium present a radiation hazard.

A newly discovered labeling technique consists in simply mixing an organic compound with a liquid tritiating reagent-a complex of tritiated phosphoric acid and boron trifluoride-in glass or polyethylene laboratory ware at room temperature.

The reagent is easily made by first combining phosphorus pentoxide with tritiated water to form anhydrous tritiated phosphoric acid, TH,PO,, into which is bubbled boron trifluoride gas to form the complex.

In addition to the advantage of convenience, this new technique does not require the use of multicurie amounts of gaseous tritium. High specific activity tracers can be produced using only millicurie quantities of the liquid reagent, although activities up to one curie per gram can also be obtained. The method is faster than any previously available; equivalent labeling can be obtained in 6 hours as compared to more than 1 week by the Wilzbach method. Already demonstrated on a variety of simple aromatic compounds, this tritium-labeling technique is potentially applicable to a major fraction of pharmaceutical and biological compounds.

SOURCE FABRICATION AND
SAFETY EVALUATION

Sealed radiation sources, hundreds of which are employed in hospitals in the United States for interstitial or teletherapy use, are continually being improved in regard to safety and utility. Leak proofness has been increased through new methods of encapsulation, while assurance against damage in fires or accidents has been accomplished through improved containment and shielding.

Cobalt 60 for teletherapy is employed in metallic form, usually nickel plated against corrosion, then double encapsulated by welding in stainless steel capsules. Cobalt

60 used in brachytherapy radiation sources may be in the form of metallic cobalt wire, bare or nickel plated, or wire made from a cobalt-nickel alloy (cobium). The cobalt wire may be encapsulated in stainless steel and sealed by Heliarc welding, or in platinum-iridium tubes or needles, which are sealed with a brazed or soldered plug. The cobalt-nickel alloy wires are generally encapsulated in stainless steel tubes or needles sealed with a small screw plug.

Cesium 137 in present teletherapy sources most commonly is used in the form of compacted cesium chloride, double encapsulated in stainless steel or monel. Although cesium chloride is soluble, it does not attack these metals and has the advantage of compactness relative to other cesium compounds.

Beta ray applicators employ strontium 90 which is incorporated in a ceramic or metal matrix, then doubly encapsulated in stainless steel and aluminum so as to leave two thin “windows,” one of each metal, for emergence of the beta particles.

In the increasingly unlikely event of containment failure, each radioactive source material itself should be in such a form as to minimize the extent of dispersal and biological absorption-that is, be "inherently" safe. The concept of inherent safety is being achieved by development of highly stable ceramic matrix materials. Proprietary ceramic and fused glass radiation sources are available commercially.

Two new highly stable matrix materials developed under Atomic Energy Commission contracts for isotopic power sources but possessing much wider applicability are (1) strontium titanate and (2) cesium "polyglass."

Strontium titanate is a high density ceramic with a high melting point and extremely low solubility. It provides an excellent way of "locking up" strontium 90 in a useful form until natural decay removes all danger of significant quantities of the radioisotope getting into the environment.

Cesium polyglass is the matrix material used to contain cesium 137 in the isotopic

thermoelectric source which will generate power for an automatic seismograph station to be used on the ocean floor. As a borosilicate glass with a high silicon content, it is unusual among substances containing large concentrations of cesium in being quite insoluble. Its specific activity, however, is not so high as that of other cesium compounds.

3,20

Since the number and diversity of uses of sealed radioisotope sources, in new and varied designs, are expected to expand continually, the Commission has undertaken a program to develop standard safety criteria for a wide range of sealed sources. Current source compositions, designs and fabrication techniques have been surveyed to evaluate source performance under a wide variety of conditions-thermal, mechanical, chemical, radiation and pneumatic-which might be encountered under both normal and abnormal conditions of use. The resulting data will help to accelerate the safe use of radioisotopes by (1) providing regulatory groups with technical guidance in establishing safe and practical regulatory practices and (2) giving manufacturers definite test goals to meet.

ISOTOPES DEVELOPMENT CENTER

Recognition of the vast potential benefits that will accrue from creative research and development on production and use of radioisotopes has led the Commission to establish an Isotopes Development Center, which is located at its Oak Ridge National Laboratory. Broadened programs of basic and advanced research in isotope technology will be conducted at the Center, which will serve as a focal point for isotope research and development. The Center plans to provide technological data to government agencies, private research groups, industry and educators to assist in expanding beneficial radioisotope applications.

The Center will embrace a complex of radioisotope facilities. It will incorporate the Fission Product Development Laboratory, which develops new methods of separating, purifying and fabricating mas

sive quantities of fission products. Chemical operations on highly concentrated fission products are carried out in shielded cell blocks containing process equipment designed for unattended control of various unit operations such as solvent extraction, evaporation and precipitation. A number of cell blocks are equipped with mechanical manipulators designed for work in intense radiation fields.

More general in purpose will be the new Radioisotopes Development Laboratory. This is located in a reinforced concrete and steel two-story structure, with a gross floor area of about 12,000 square feet. The building will contain four hot cells, a cell-operating area, laboratories, offices, change rooms, storage and utility areas and a three-level chemical engineering area. The laboratory will undertake to advance the development of new processes to improve the availability, purity and diversity of many usable isotopes for research, industrial and medical applications.

Other facilities available to the Isotope Center include stable isotope separators, radioisotope production accelerators, and the Oak Ridge National Laboratory reactors, providing the Center with one of the world's most comprehensive array of research and development laboratories, together with a broad reservoir of technical and scientific ability for furthering isotope progress.

CONCLUSION

Radioisotopes have already made important contributions to basic research vital to nearly all areas of medical progress, to the development of unique diagnostic methods used on millions of patients, and through therapy to the useful prolongation of hundreds of thousands of lives. Nevertheless, opportunities are still expanding. With the increased incentives created by advancing medical needs, progress will be accelerated in the production of isotopes and labeled materials. Concurrently, the almost unlimited possibilities for unique isotopic materials will stimulate creative

22-502 0-63-pt. 6-24

thought toward developing new and wider usage.

Division of Isotopes Development
U. S. Atomic Energy Commission
Washington, D. C.

I wish to express my appreciation to Mr. Arthur F. Rupp, Director of the Isotopes Development Center at the Oak Ridge National Laboratory and his staff for furnishing suggestions and specific data. Mr. Gifford A. Young of my Division also has been most helpful in reference research.

REFERENCES

1. AEBERSOLD, P. C. Development of nuclear medicine. Am. J. ROENTGENOL., RAD. THERAPY & NUCLEAR MED., 1956, 75, 1027–1039. 2. AEBERSOLD, P. C. Cyclotron: nuclear transformer. Radiology, 1942, 39, 513-540. 3. AEBERSOLD, P. C., and HrrсH, J. W. Develop

ment of safety performance tests for radioisotope sealed sources and devices. Health Physics, 1961, 7, 117-119

4. BEIQUE, R. A., and LOUGHEED, M. N. Considerations of shielding for cesium-13′′ sources, containing cesium 134. Radiology, 1961, 77, 281-283

5. BREZHNEVA, N. E., and OZIRANER, S. N. Radioactive isotopes and their production under neutron irradiation. International Atomic Energy Agency Review, 1961, 15, PP.

70.

6. CASWELL, A. E. Laboratory production of short lived radioisotopes. Am. J. ROENTGENOL, RAD. THERAPY & NUCLEAR MED., 1962, 87, 183-184.

7. Electronuclear Research Division Annual Progress Report, 1961, ORNL-3083, p. 80.

8. ENDLICH, H., HARPER, P., BECK, R., SIEMENS, W., and LATHROP, K. Use of I25 to increase isotope scanning resolution. AM. J. ROENTGENOL, RAD. THERAPY & NUCLEAR MED., 1962, 87, 148-155.

9. GREEN, F. L., CHEEK, W. D., BLACK, R. E., and GRAHAM, G. P. Samarium 145, samarium 153, gadolinium 153 and thulium 170 sources for radiography. Nondestructive Testing, 1960, 18, 382-388, 402.

10. HARPER, P. V. Characteristics and manufacture of radioisotopes for medical purposes at Argonne Cancer Research Hospital. Fifth Nuclear Congress, Rome, Italy, 1960, June

20-26, pp. 53-58. Office of Technical Services, U. S. Department of Commerce, Washington, 1960, Report TID-7601, p. 96.

II. JACKSON, F. L., KITTINGER, G. W., and KRAUSE, F. P. Efficient tritium labeling with electric discharge. Nucleonics, 1960, 18, 102-105. 12. MARTIN, J. A., LIVINGSTON, R. S., MURRAY, R. L., and RANKIN, M. Radioisotope production rates in 22 mev. cyclotron. Nucleonics, 1955, 73, 28-32.

13. MYERS, W. G., and VANDERLEEDEN, J. C. Radioiodine-125. 7. Nuclear Med., 1960, I, 149–164. 14. RICHARDS, P. Survey of production at Brookhaven National Laboratory of radioisotopes for medical research. Fifth Nuclear Congress, Rome, Italy, June 20-26, 1960, pp. 41-52. Office of Technical Services, U. S. Department of Commerce, Washington, 1960, Report TID-7601, p. 96.

15. ROSENBLUM, C. Chemistry and application of tritium labeling. Nucleonics, 1959, 17, 80-83. 16. RUPP, A. F. Large-scale production of radioisotopes. First International Conference on Peaceful Uses of Atomic Energy, Geneva, United Nations, N. Y., 1955, 8/P/31417. Rupp, A. F. Reactor production of radioisotopes. Monograph to be published by Pergamon Press.

18. RUPP, A. F., and BINFORD, F. T. Production of radioisotopes. 7. Appl. Physiol., 1953, 24, 1069-1081.

19. Special sources of information on isotopes. 1962, TID-4563, p. 82. Available from Division of Technical Information Extension, U. S. Atomic Energy Commission, P.O. Box 62, Oak Ridge, Tennessee.

20. TOWNLEY, C. W., FACKELMANN, J. M., SELANDER, C. L., EWING, R. A., and SUNDERMAN, D. N. Development and evaluation of safety performance criteria for sealed sources. Office of Technical Services, U. S. Department of Commerce, Washington, 1961, Report BMI-1559, p. 88.

21. Tritium tracing rediscovery. Nucleonics, 1958, 16, 62-67.

22. VANDERLEEDEN, J. C. Development of counting techniques for low energy gamma radiation for applications in biology. Thesis, Ohio State University, 1959

23. WILZBACH, K. E. Tritium-labeling by exposure of organic compounds to tritium gas. J. Am. Chem. Soc., 1957, 79, 1013

24. YAVORSKY, P. M., and GORIN, E. New methods of tritium labeling of pure compounds and coal derivatives. Paper presented at 141st National Meeting, American Chemical Society, Washington, 1962, March 20-29