Radioisotopes in Medicine (1958)

[Music] on December 2nd 1942 an event took place in Chicago which was destined to change the lives of each one of us this small group of men working in deepest secrecy under the leadership of enrio fary achieved at this spot the first sustained nuclear reaction and thus the power to produce neutrons in unlimited numbers it is a matter of historical record that one of fy's first thoughts was the possibility of using these neutrons to prepare Isotopes for use in medicine it was only 2 years later in a suburb of this same city that Abbott began its studies with radioactive penthol just why was such a substance an anesthetic and how did it behave in the body how could its action be further improved radioisotopes did indeed help provide the answer this work also emphasized the possibility that there would soon open up an entirely new and virgin field of radio Pharmaceuticals radio isotopes for medical use as they come from a nuclear reactor cyclotron or radiochemical plant require still further processing purification assay and often conversion to proper pharmaceutical forms before they are ready for use this has posed a challenge to those engaged in radio pharmaceutical work the answer has been the development of many new handling techniques new products and new pharmaceutical forms i131 has assumed a commanding importance in medicine it is currently produced only in the Oak Ridge reactor and converted to a solution of sodium radioiodide a portion of this unrefined material is transferred as needed to the nearby Abbott radio Pharmaceutical Plant this morning supply of i131 shielded with 200 lb of lead contains the equivalent of about 10 G of radium radio Gold radio Cobalt and several other items were obtained at the same time in the laboratory one of several devoted exclusively to work with this particular isotope the bottle of crude i131 is moved to a heavily Shield yielded but still easily accessible area inside a stainless steel Hood Alo quats of the solution are removed as needed for purification the preparation of various pharmaceutical forms or the synthesis of organic compounds extensive use is made of radio assays which are more rapid more convenient and more accurate than any chemical method assay of the gamma activity preferably is done with the lorit and scope in which the operator times the rate of the fall of a quartz fiber across a visual field beta rays are assayed in absolute terms using a geiger counter and scaler the activity being in the form of an infinitely thin evaporated sample aluminum absorbers are interposed to help establish the purity of the isotope the assay sample is saved for measurement on many successive days to determine the half life again as a check on radio chemical Purity with all of these assays carried out on the material as received and on every batch of every product made from it the activity contained in any given volume subsequently dispensed or packaged can be stated accurately each radio isotope gives off a spectrum of rays of different energies this complex electronic system automatically measures the complete gamma spectrum of each lot and provides a permanent graphic record of the radiochemical purity of the radio Pharmaceuticals made from it to establish the absence of other chemical forms of i131 tests are made by means of paper chromatography the sharp intense Peak and the absence of other Peaks indicates that all of the activity is present as iodide when all such tests show the desired degree of purity the Isotopes are released for further processing and use until recently Isotopes were handled and dispensed only in liquid form then came the idea of administering various radioisotopes as capsules a method was developed in which the radioactive material is plated as an invisible layer on the interior wall of a high strength gelatin capsule from which it cannot Escape or cause contamination to all appearances such capsules are completely empty here is how the procedure is carried out an accurately known amount of radioactivity sufficient for many thousands of capsules is purified and converted to a form from which it will deposit quantitatively in the capsule during processing this is transferred in its Shield to the encapsulating room in the meantime the gelatin capsules have been separated and the bodies placed in shielded trays while five colors are used for activity identification we shall follow today's production of red capsules each to contain approximately 100 microcuries the heart of the process is this specially designed machine the operator wears two visual radiation detectors and a film badge which provides a permanent record of the nominal radiation received in spite of the heavy shielding of the instrument itself a Twist of the right wrist moves the capsules horizontally and the foot motion lifts them into proper position to receive the isotope behind the Leed glass protection is a device which dispenses an accurately known amount of i131 activity in carrier free form into each capsule after one row is filled a movement of the left hand positions the next row for filling the trays are then placed in this device which completes the procedure whereby the material is caused to adhere firmly to the interior wall of the capsule this unit is designed to produce several thousand capsules in a working day even though the capsule contains no liquid each is tightly sealed so that even if dropped no harm or contamination will result each has been so treated as to resist even this bending test Which is far more strenuous than would be encountered in clinical use for the first time in pharmaceutical practice every capsule is individually assayed during production this is only possible because the gamma ray activity permits assay from outside the capsule without damaging it in any way a robot counter takes each capsule from a shielded Hopper positions it in front of the cellation counter located behind one of the instrument panels assays it within a tolerance of 5% records the count and places it in the shielded jar designed to receive capsules counting in that range the robot working day and night is essential if all capsules made in one week are to be ready for shipment some 5 days in advance of the official calibration date capsules are taken at random from the jars at various stages of the run and subjected to quantitative assay the counting system is purposely made similar to that employed in clinical practice The observed values are 100 100 97 102 and 98% of the standard the end result of this week's effort is five jars of i131 capsules ready for distribution each preparation made during any 5we period is of a different color this color coding prevents confusion both at the point of production and in the user's Laboratory such capsules Decay to approximately 1 half their original strength in 8 Days hence a shipment frequently consists of three or more activities to be used on successive weeks as they in turn reach the appropriate activity for administration for the convenience of the user they are pre-calibrated for Wednesday following the day of shipment here for instance is a teletype request from the isotope laboratory of William Bowmont Hospital in Royal Oak Michigan for five different items even though the order has arrived just before noon all materials will be sent out that same evening by air express and will be in the hospital ready for use the next morning had the order originated in Geneva Oslo or Honolulu not more than 20 hours additional would be required for the delivery of the urgently needed material the teletype order is converted to precise laboratory and shipping directives assays are are calculated for 24 hours after shipment so that the correct activity will be present at the time of administration to the patient in the production section this young lady fills the order from stocks on hand each vial will contain an appropriate number of capsules of known activity these four vials shipped together will care for all of the i131 diagnostic cases to be handled in that hospital for the next 3 to 4 weeks the application of the principle of color-coded capsules to therapeutic doses required several years of additional study and the preparation of an even purer i131 in this case the i131 capsule is assayed at the moment of preparation three strengths are prepared one three and five mures so that through the use of a suitable comb of capsules the same flexibility of dosage is possible as with Solutions here because of the higher activity involved a lead Shield is required in spite of this the weight of the shipping box is still less than 4 L pounds the components of the order namely filled boxes invoices and shipping documents meet in a packaging room as it emerges each box passes in front of a cellation counter which measures the radiation emitted thus the final package though sealed attests that it contains the proper amount of activity and meets all shipping requirements regarding exterior radiation to minimize exposure of workers portions of the packaging line are shielded and the packages are transported along the ceiling to the truck waiting outside the door the order received just before noon is ready ready by 3:30 all parts have been prepared assayed the way bills written the order is on the way to the Knoxville airport for loading onto the first available plane it will be in Detroit by 11:00 p.m. approximately 12 hours after receipt of the order similar operations have been proceeding simultaneously in North Chicago to prepare and dispatch the radio Pharmaceuticals leaving from there for William Bowmont hospital this institution maintains a radioisotope department typical of those found in hospitals throughout the United States it is capable of carrying out a wide range of Diagnostic and therapeutic procedures some of these are to be found on this morning's worksheet the first patient has an anemia of unknown iology to carry out the Shilling test he has given a capsule of Cobalt 60 labeled vitamin B12 2 hours later 1 MGR dose of inactive V12 is injected to ensure maximal excretion of the activity in the urine and 24-hour specimens collected activity in a 1,000 cubic cm sample may be determined easily by setting the bottle containing the urine directly in contact with the crystal of a thoroughly shielded probe ctil The observed output of 4% is indicative of poor absorption the test is repeated now including in addition ition a capsule of intrinsic factor the new output is found to be 12% which is in the normal range providing a highly probable diagnosis of pernicious anemia this test being independent of the patient's previous therapy provides an easy means of securing a conclusive diagnosis a second diagnostic procedure makes use of the i131 derivative of a chemically pure fat triolian this material is available as capsules embedded in an oil absorbent medium capsules may also be prepared just prior to use by adding to each an amount of tagged fat equivalent to 25 to 50 microcuries at the same time an identical amount is measured into a plastic lined stool collection container in which have been placed 100 to 200 cubic cm of oil to simulate stool volume this acts as the standard the capsule is administered and the stools collected in 24-hour units counting is carried on from outside without opening the cartons in this instance a 48h hour output of 20% was found well above the normal range of 2 to 3% the test is repeated using this time an iodine labeled OIC acid which does not require pancreatic enzymes for its absorption the lower value of 5% obtained on repeating the test suggests the presence of pancreatic disease thyroid studies with i131 are the most common of all isotopic procedures as is customary the clinician interviews the patient establishes that there are no contraindications and decides that she is a suitable candidate at the laboratory she has given a capsule containing approximately 25 microcuries of sodium radioiodide this is taken like any other capsule a notation is made in the hospital records and instructions are given to report at a definite time it has been shown that absorption from such a capsule is more rapid than if a solution had been given if the patient had been from an area some distance away it would have been customary for the physician to give the capsule to the patient to be taken at home at the appointed time the patient is seated in a chair with her head firmly positioned a probe cator connected to a suitable scaler is placed at an accurately established distance in this case 20 cm from the front of the patient's neck a count of approximately 2 minutes is made the direct radiation from the thyroid is eliminated by covering the latter with a 1/2 in thick be Shield a repeat count therefore measures the body background only this is is subtracted from the initial reading to secure the true thyroid count a suitable Phantom is needed to simulate the absorption and back scattering in the neck this one was developed recently by the Oak Ridge Institute of nuclear studies a capsule from the same lot and therefore the same color as that given the patient is placed in the Phantom a 2-minute count again is made if the B Shield is now swung into place over the Phantom we secure by subtraction the true Phantom count the thyroid count divided by the Phantom count gives us directly the percent of the administered dose in the thyroid at that time by convention this is known as the thyroid uptake the time after Administration selected for the first measurement is usually between 2 and 8 hours this study is particularly valuable in detecting hyperthyroidism if there is any doubt as to the diagnosis or if a therapeutic dose is to be given the 24-hour thyroid activity is again measured in this same way absorption is usually maximal by this time many clinicians prefer to determine in addition the urinary output the protein bound iodine conversion ratio and to carry out a scanning procedure as auxiliary tests to Aid in achieving a correct diagnosis it is is to be emphasized that the thyroid uptake in itself is but one part of a broad spectrum of valuable tests all available if i131 is used as a diagnostic agent the assembled data is discussed by the radioisotope director and the clinician who decide upon what further steps may be desirable diagnosis in this case is hyperthyroidism and it is agreed that a therapeutic dose of 6 mures of i131 will be administered in capsule form these two therapeutic capsules taken together contain the prescribed dose they are administered in exactly the same way as the diagnostic capsules the final case not only makes use of i131 but provides an excellent illustration of the fact that i131 often localizes in a barent and metastatic lesions scanning with a guer mu tube directly in contact with with the skin shows a significantly increased count over a circumscribed area in the left scapula and demonstrates that the lesion is of thyroid origin such a diagnosis and localization would not have been possible by any other means a mechanical scanner may be used to make a pictorial record for the use of the surgeon or for further comparison after treatment it is decided that the preferred mode of treatment is the oral administration of 50 mures of sodium radio iodide all operations are carried out in a stainless steel tray The Shield cover is removed with a long mechanical finger the bottle cap is grasped and unscrewed with a shielded device the patient drinks directly from the bottle through a straw a stream of water ensures The Taking of the entire dose yeah this way the entire procedure may be carried out without significant exposure to operator or attendant Personnel simplified techniques and instrumentation such as those which we have seen together with the availability of Diagnostic and therapeutic radioisotopes in easily employed pharmaceutical forms are rapidly making isotopic procedures available to Physicians trained in the use of these important new tools of Medicine [Music]