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B. Scatter radiation measurements at the University of Paris
In France I spent 2 days at the University of Paris, mostly at the Institute Gustave Roussy, which, according to many European observers, is the most isotopically active French outfit. The other centers in Paris have no observable activity and one institute seemed to be actively opposed to the use of any isotope other than radium.
Dr. Tubiana and Dr. Dutriex are doing considerable work with iodine 131. There is nothing unusual except in the way of physical measurements. They have a moderately large laboratory with basic equipment for work with carbon 14, iodine 131, P 32, and gold 198. Very little is being done as yet with gold 198. The carbon 14 work is the usual chemotherapy tagging problem. In the laboratory there is a good iodine 131 loading and diluting device that has been cleverly designed. The P 32 dry box is a routine device. The rest of the laboratory is primitive by our standards but workable. They seem to be applying tremendous amounts of protection, much more than is necessary for the levels of hazards they work with.
Dr. Dutreix has an iodine 131 uptake measuring device that is working well and Is giving good results. A large tray is carried by a double tube stand placed over the bed. This tray has four 1.5 cm. lead diaphragms, and positions are set with wooden sticks. The area shielded is considerable and probably adequate with the additional shielding of the Geiger-Muller tube. They are using this machine not only for quantitative iodine 131 pickup studies but also, at a tremendous expense of time and effort, they are using a very small focal spot manually adjusted over the area in an attempt to get multiple-survey type profile measurements. It takes one-half day to get what our scintogram shows to be an inadequate survey. Dr. Dutreix is cognizant of the faults of his equipment and is not being held back by the lack of ideas but rather by lack of time and funds. Drs. Tubiana and Dutreix and a physicist are extremely interested in the measurement of the scatter component of radiation from internal sources. Using wax and water as phantom material, they are working on the buildup of scattered radiation within a polyvinyl right-cylinder phantom. The phantom is kept at a constant temperature by a heating plate that is used both for melting the wax and keeping the temperature roughly constant. There are templates for positioning chambers and sources in various positions inside of the phantom. Radium was being used as the source while I was there; however, iodine and other sources have been used. The measuring devices are small spherical chambers 1 mm. thick and have a 1 mm. open space and a spherical collector inside. They are said to work with considerably greater uniformity than the Baldwin-Farmer chamber. All are standardized against radium.
The problem of the scattered radiation component is being approached primarily by blocking the direct-primary component. In the phantom they place a lead shield shaped to block only the primary rays between the source and the detector. The radiation within the umbra of this shield should be a good direct measure of the scattered radiation. Their preliminary work indicates a surprisingly large buildup of scattered radiation intensity at a distance from the source, and as in keeping with K. Z. Morgan's statements on the I D2/D plots of intensity around large sources in air and water. The buildup factors seem to be remarkably high and there are many details of technique in the mesaurement which are, in my opinion, open to criticism. Using shielded areas, we have attempted the same type of measurement following an idea of Gray's which appeared in the literature many years ago, and have already made many measurements on isodose lines around sources in various media. It seems worthwhile for us to reconsider the inclusion of the type of measurements adopted by Tubiana's group. There was a considerable discussion on the effect of adding a proportion of higher Z scattering material within the system. Rather than approach the problem the way we are doing it they have built their phantom so that a series of bones can be added as an increased scattering material. C. Meeting with Dr. Bush on internal dosimetry
On Saturday afternoon Mr. Eastwood of Harwell and I had the opportunity of a conference with Dr. F. W. Bush on the problems of dosimetry from internal sources. Dr. Bush is best known in this country for his theoretical work on the distribution of radiation from various types of sources. He is, however, a practicing diagnostic radiologist and does all of his theoretical radiation physics in his spare time as a hobby. Everybody who knows him has agreed that he is a genius in the mathematics of radiation dosimetry.
Dr. Bush was well acquainted with the faults of the present system of calculating radiation dose but pointed out that before any theoretical determination is possible certain experimental facts are necessary. I described the studies we are attempting in phantoms and he agreed that while these were of immediate practical importance they did not allow for a study of the theoretical patterns from which a theory of dosimetry could be devised. In the course of the discussion we tried to outline what types of phantom measurements would be desirable for a definitive study. In the problem of the isotopes (such as intracavitary gold 198 and other colloids) that absorbed on surfaces we came up with the idea of using a flexible long-line source. This source could be bent into any shape and converted by rotation into a solid of revolution, thus allowing for the study of the radiation around both internal and external shells of various sizes and dimensions. The question of the sodium-benzoate system was also opproached. If such a chemical-dosimetry system could be gelled it might be possible to test empirically the distributions of rotating fields. Dr. Bush would very much like to have copies of our data and will attempt an independent analysis of the results. He was also interested in the problem of the deviations of absorption from that predicted by theory in low Z materials common in tissue and would like to participate in the study of whether such differences could account for a portion of the differential radiation sensitivity of tissue.
D. Activities in Zurich
The visit to Switzerland was spent entirely with Dr. Muller, of Zurich. Dr. Muller described his work on the state "O" cancer of the uterus for which he would like to use a beta applicator. Muller has tried to get Tracerlab to design him a strontium applicator but so far has not been successful. It is difficult to see how a strontium applicator could be made to fit into the long thin probe desired by Muller. The use of ruthenium 106 might be far more practical. It might be worthwhile to consider the manufacture of such an applicator.
With the help of very fancy surgical techniques Muller is spending a great deal of time on the mechanical methods of localization of radiocolloids. They are doing such things as introducing the radiocolloids into the cisterna magna, and letting them drain through the spinal canal out through a lumbar puncture. Although the method is tedious and time consuming he thinks it is perfectly safe and has an important, though limited, field of application.
Muller suggested the use of microembolization many years ago and is still working on it. He thinks it gives a far better distribution in such things as irradiation of a lung, but his method of measuring the distribution inside of the body is by the use of external autoradiograms with ordinary X-ray films. This method has almost no resolution and I doubt that a scintiscanner record would confirm his clinical impressions. He is impressed with the excellent distributions of the carbon plus radiogold microemboli given intravenously for localization in the lungs.
The history of Muller's invention of the intracavitary gold technique is an interesting one. Before World War II he spent some time touring America and visiting various centers where there were cyclotrons. During the war he had the Zurich cyclotron available for use and began with the manufacture of a zinc isotope. The early work was done in the spring of 1945 in which he injected a radioactive zinc colloid into a mouse. The first autogram of this intracavitary distribution appeared in print shortly thereafter. So far as Muller knows the original reference to the intraperitoneal application of nonsoluble particles of radioactive material appears in the Muller article in Experentia (vol. 1-6, p. 199, Sept. 15, 1945). The autograms of the mouse shown on page 199 is the first published application of nonsoluble particles in an animal. On page 200 of the same article he shows an autogram of the material, zinc 63, in a patient. He mentions in this same article the possible use of other isotopes that might give a better radiation pattern. In succeeding articles in the same journal in 1946 and 1947, Muller described the injection in the parametrium of a few patients, and apparently was the first to suggest an interstitial use. his first article he makes the suggestion that the size of the particles are of primary importance. In 1946 he first developed the idea of microembolization in which radioisotopes were given intravenously to get a good localization in the lung.
E. Current activities at Heidelberg University
At Heidelberg University Prof. J. Becker and Dr. K. E. Scheer have probably the most active isotope therapy department that I saw on the Continent. Becker and Scheer have manufactured a number of 6-millimeter beads of cobalt. Each one of these beads is turned out individually on a lathe and has a hole drilled through it. They are irradiated at Harwell to an intensity of 1 or 2 megacycles per bead and then plated to a thickness of about 50 microns of gold after irradiation. To my questions on the permanence of the gold-plating Dr. Scheer demonstrated by sterilizing a gold bead in boiling water and in 'baths of hydrochloric acid. He has never been able to detect a loss of cobalt 60 through the gold. In spite of this, however, he would rather use a cobalt nickel alloy for the bead, but cannot get the material. The beads are handled with a simple forceps system, are strung on a wire, and pushed through a large trocar, into maxillary sinuses, uteri, and bladders. Radiographs demonstrated excellent and reproducible patterns of the beads within cavities. The dosimetry can be adjusted by interspersing the active beads with inactive aluminum beads. Dr. Scheer has developed a simple cadmium sulfide crystal dosimeter on a rotating table to determine the isodose lines of various patterns of beads. The beads are also used to manufacture plaques on a plastic mass. Since these plaques, however, did not give a satisfactory distribution of radiation, Becker and Scheer are also using powdered cobalt, and mixing it with plastic moulage material. The powder is well distributed within the moulage plastic and the outline of various surface lesions are copied under a piece of cellophane and shaped in depth to make various types of surface applicators. The material is rolled out on a breadboard with wooden spoons and shaped to fit any surface. It is covered with a hydrophilic cellophane covering and strapped into place with adhesive tape. They have never been able to determine a loss of cobalt with this method but they would far rather use a small bead than the powdered cobalt.
In order to get away from the use of the powder, Dr. Scheer has developed a system for making small plexiglass pearls. The powdered cobalt is irradiated to low intensity at Harwell and is placed into a solution of methacrylate. When well mixed the methacrylate solution is placed in a -10° C. water bath, the material is forced out of a small opening into a cold bath of glycerin layered in water. The small droplets form themselves into approximately 2-millimeter pearls, each containing a small amount of cobalt. These pearls are used in various ways. They are either mixed in a plastic moulage material or can be suspended in various liquids. If the liquid has a high specific gravity, the pearls will float on the top and can be positioned inside of a cavity. With low specific gravity they will fall to the bottom or with the correct specific gravity they can 'be made to distribute themselves throughout the fluid.
Becker and Scheer have investigated the dosimetry around such small plexiglass pearls mixed into various shaped plastic masses. While the isodose lines do not approach the cosine surface theoretically obtainable, they do get cups of radiation that almost approach this ideal. The idea is an excellent one and should be followed up.
Dr. Becker has just completed the construction of a large isotope laboratory, complete with shops, chemistry, physics, storage, and therapy rooms. A 15 mev pendulum therapy betatron is being installed within the next few months. They have space for a cobalt 60 machine in which they would like to have complete freedom of rotation, but do not have sufficient funds to purchase the machine at the present time.
At Heidelberg they are doing the usual work on iodine and phosphorus therapy but on a small scale. Becker and Scheer are specializing primarily in the external source applicators of low specific activity. In their spare time they are editing the world literature on radiotherapy in the journal Zentralblatt für die Gesaurte Radiologie.
F. Cyclotron-produced isotopes from Holland
In the Phillips Technical Review (vols. 12 and 14), there has already been published some details of the Amsterdam synchrocyclotron. Halberstadt gave a short description of the machine as it is being used for the production of carrierfree, cyclotron-produced radioisotopes for clinical use.. He also described some of the separation techniques and their yields and described some of their methods of absolute standardization by measurement of the characteristic X-rays with a specially made Geiger tube. In table 2 is presented a list of the isotopes and the yields that are now being produced in Holland and are ready for distribution.
Yields of radioisotopes produced in the Philips synchrocyclotron with 30 mev. deuterone and a mean beam intensity of 30 microamperes
Saeland (Lillestrom, Norway) in cooperation with the Dutch, described the operation of the Dutch-Norwegian joint establishment nuclear reactor at Kjeller, Norway. Their reactor has been in operation for a half year with a mean neutron flux of between 10" and 10". Although the reactor was primarily built for experimental use it is well designed for a large-scale production of radioisotopes, and they have decided to establish a routine production program. They do this by contract with pharmaceutical firms; and they are now preparing the details of their distribution system for iodine 131, phosphorus 32, gold 198, and a production scheme for cobalt 60. This paper was another indication of the intense competition that is now going on for the sale of radioisotopes in Europe. G. Diamond probe counter
One of the few interesting gadgets that was being demonstrated was a flexible probe counter developed by the Diamond Producers Association (head office, Consolidated Building, Kimberly, South Africa). We were shown a demonstration of the fluorescence of various diamonds under ultraviolet light which allowed the determination of which would and which would not serve as detecting devices for gamma rays. A long, thin, flexible probe counter that they have developed is still considered by them to be an experimental instrument. It is, however, now commercially available. The diamond was an extremely small volume and appeared to be a fine pinpoint counter. It could be liquid sterilized or autoclaved, and used internally. It functions well at room temperature and, they thought, at much higher temperatures. The claim was that good counting diamonds (not all diamonds are good counting diamonds) maintain a steady counting rate for several hours. They also have the usual associated electronic equipment especially adapted for medical use. The idea is an interesting one and it is worth further investigation.
VII. AUTOMATIC SCANNING METHODS
At the Royal Cancer Hospital I saw the machinery that has been set up by Mayneord, Evans, and Neubery for mapping the distribution of radioactive isotopes. The model presently under construction is so far superior to our scintiscanner and the 2 or 3 other methods that I have heard of in this country, that I think the problem should be reinvestigated. Mayneord and his associates have constructed a mechanical device that in 6 minutes carries a detector over
a planar surface in a rectangular scanning pattern covering an area of about 30 by 30 centimeters. It is so designed that the speed may be increased or decreased. The field size can easily be made much larger or be cut down to a small field of scan. On this mechanical scanning device any sort of detector may be attached. For scanning internal isotope distributions a scintillation crystal is used. They use a different detector for ultrasonic waves. Many other types of detectors are planned. The electrical impulses from the detector mechanism are amplified and are routed through a series of amplifiers and storage tubes and finally displayed on a television screen. Prior to the presentation of the final picture of the complete scan, background and interferring line noise is determined electronically and subtracted from the final picture which has a remarkable resolution and is relatively close to that theoretically obtainable under the best possible conditions. Plans are under way for the adoption of this basic mechanism into a large number of scanning problems. It is theoretically possible to do quantitative scanning, although this has not yet been attempted. The limitation of the areas of scanning by the use of visible light beams can be superimposed and will be in the future. One of the immediately practical improvements of the device is the attachment of a siamese twin moving container underneath the patient. On this container there would be placed a radioisotope source of any particular energy desired. The present plan is to use thulium with an 85 kev energy. A combined collimated low-energy source and a collimated scintillation detector will yield a high degree of resolution. Such a device reopens the field of diagnostic roentgenology with radioisotopes. The machine, except for a few minor bugs, is almost ready for routine operation and will, I bebelieve, outclass and throw every other piece of scanning equipment out of date.
VIII. PAPERS REPORTED ON THE USE OF RADIOACTIVE ISOTOPES
E. A. Jochin, of London, presented his impressions on the response of thyroid carcinoma to radioiodine treatment based upon a series of about 20 patients. He felt that one of the most important problems was that of measuring the response of the thyroid carcinoma to the treatment. He outlined his impressions of a number of methods of determining this response: (1) He thought serial biopsies were rarely justifiable. (2) He felt that local edema and tenderness of a gland shows evidence of iodine uptake rather than of radiation change. (3) He felt that the reduction in the size of the metastases as determined by any available method, although a measure of effect, did not give an indication of residual function. (4) He felt that the decrease in the rate of thyroxin formation was shown by a progressive lowering of the protein bound radioiodine concentration developing after successive test doses. (5) It was his feeling that the most useful measurements of response to treatments may be made by a profile counting method. He believes that the external counting procedures often showed that the turnover of radioiodine in a carcinoma may be faster during the therapeutic dose than during the preceding test dose. He felt that this indicated a radiation effect. Pochin felt that the aim in the treatment of his cases has been to reduce the total tumor uptake of radioiodine below 0.5 percent of the test dose. Rotblat and Rollinson (London) described a clever apparatus for determining the uptake of radioactive iodine in the various organs of the body as a function of time after its intravenous administration. The system was stimulated by means of a simple electrical circuit in which a condenser is charged and discharged through a path of least resistance network. By varying the electrical constants of his circuitry he could simulate many of the conditions of iodine metabolisms and felt that the system helped in making a diagnosis of the state of thyroid function of a given patient.
Along with Owen, Rotblat also presented a survey of various methods of using iodine 131 for the determination of thyroid functions. He felt that most of the present methods failed to give the answer in cases that most needed an objective test. It was his feeling that the analysis of the urinary excretion provided the most accurate discrimination between the states of euthyroidism and hypothyroidism and also gave information on problems of iodine space and effects of antithyroid drugs.
Horst (Hamburg, Germany) presented his experience with 200 patients with thyrotoxicosis studied with iodine 131. All of his dosimetry was stated in terms of rep per gram, but he failed to state how these doses were determined.
Abbatt and Frazier (London) described 70 cases of thyrotoxicosis treated at Hammersmith Hospital with a single radioiodine dose in patients first controlled with thiouracil. In a clinical assessment after 1 year following the single-dose method of treatment, 75 percent showed satisfactory remission, 23 percent