Diagnostic Procedures with Radioisotopes

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TRACERVIAL DIAGNOSTIC 1-131 SOLUTION This illustrated Loose-Leaf Manual is designed to provide a compact source of technical information for those currently using, or desiring to use Radioisotopes in Diagnostic Procedures. Department of Radioactive Pharmaceuticals North Chicago, Illinois Oak Ridge, Tennessee

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Oak Ridge Nuclear Reactor Where One Of T h e Laboratories In The Plant At Oak Ridge, Tennessee. .sotopes Are Produced As Bulk Chemicals. .t 1s Also Used For Special Irradiations. Abbott Radioactive Pharmaceuticals The Simple And Convenient Package Of acervial Diagnostic Radio-Iodine Solution. Similar Packages, With Heavy Shielding, All Abbott Radioactive Pharmaceuticals Are Supplied In Standardized Sterile Forms Not Requiring Processing Or Are Used For Therapeutic Shipments. Assay By User.

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(I) DETEKMINATION OF THYHOID FUNCTION WITH RADIO-IODINE (1-131) This test is based upon the well established ability of the thyroid gland to concentrate iodide, given orally or intravenously, to store i t first in inorganic form, and to convert it more os less rapidly to thyroxine. The latter is released into the circulation, in the form of a thyroglobulin complex, which behaves like a typical protein. Some types of thyroid tumor cells normally show little glandular activity; conversely, hyperactive thyroid areas may exist in an otherwise normal gland. These phases of biologic behavior are controlled by different mechanisms, and the study of each may contribute significantly to the elucidation of the clinical condition of the patient. On the other hand there are definite practical limits to the time which can be spent on such a test used as a hospital routine, and the problem thus becomes that of selecting the procedure o r procedures which give the most worthwhile data. The use of several different tests 1s of more Value in questionable cases than frequent repetition of any single test. I t 1s generally agreed that the Radio-Iodine uptake avoids many of the inherent shortcomings of the B.M.R., particularly the effects of environmental conditions, and the wide fluctuations seen in normal patients. The cooperation of the patient is not required, and the actual carrying out of the measurements can be done by a qualified and experienced technician once detailed procedures have been established. AS will be seen later, modern techniques for the diagnostic use of Radio-Iodine do not require special facilities beyond those available, o r easily made available, in the hospital, the clinic,or even a Well equipped private Office suite. Illustration (1) shows a typical radioisotope room suitable for the hospital having 200-400 beds. This may be supplemented by a small storage and/or laboratory area. I t is impcjrtant that this diagnostic area be sufficiently far from the X-Ray equipment, and from large sources of radioactivity, (including patients being given therapeutic doses) so that the "background" is low and constant. Measurement of urine and blood samples may be carried out in an assigned section of the hospital laboratory, providing there is no interchange of equipment and glassware. There is no need for the collection o r special deposition of excreta. Patients, if otherwise able, may be ambulatory at all times. According to A . E . C . recommendations, training of the physician for thyroid diagnosis only, must include at least thirty hours of work in a hospital allocated to use 1-131, and participation in the management of not less than ten clinical cases. Before the start of the test, the patient should have been examined by a physician, and it should be definitely established that he is not on iodide o r thyroid therapy, not been receiving medication containing any material, such as propyl thiouracil, or even certain cough medicines, o r vitamin preparations, containing iodine, which would influence thyroid uptake. iodine containing gall bladder dyes o r , of Urokon o r Diodrast, which make the uptake unreliable for at least several weeks. The use of an iodized oil precludes the test for It is assumed that techniques and instrumentation are adequate and the work conscientiously A common source of difficulty is the recent use of one of the

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A . The Simple 24 Hour Uptake This may be looked upon asa "basic" technique which is relatively simple to carryout, and which provides a reliable answer in the majority of uncomplicated cases. (a) The patient is given a dose of Carrier free Sodium Radio - Iodide (1-131) orally,in sucha manner that all of the dose reaches the stomach and is retained.This is most efficiently and simply done by the use of Radiocaps(R) - sealed units containing a carefully calibrated amount of reduced Radio - Iodide adsorbed on to the inner wall of a soluble gelatin capsule.This is followed by several glasses of water. The capsule dissolves readily. (See illustration 2,3 & 4,p.9 (15, 25 & 50 uc.capsules available.) The iodide is rapidly absorbed from the gastrointestinal tract and save for the possible omission of the breakfast before the dose, no dietary or liquid restrictions need be The dose selected will depend upon the sensitivity of the detector, and the distance from the thyroid at which the counting is done.Witha modern scintillation counter 15-20 uc. is ample.Witha TGC 8or Bismuth Cathode tube 25-50 uc. is preferable. (The dose is reduced proportionately for children.)It is anticipated that detectors with lower SenSiti vi ties will ultimately be replaced,orat least supplemented,by a scintilla tor,to keep dosage ata minimum. Certain groups are currently using as little as 1 - 2uc., on the basis that this permits prompt repeat measurements t o be made. This can be achieved only by either reducing the tube - neck distance to5 or 6centimeters, or by using highly sens i - ti ve detectors which in turn accentuate shielding and background problems. (b) The patient returns 24 hours later and is so positioned that the detector "looks" directly at the thyroid area froma known distance which is carefully maintained during all measurements. The patient may be erect, as illustrated(51,or reclining. With a scintilla tor,counting of both the standard and the patient ' s thyroid should be continued for a sufficient period to accumulate 5,000-10,000 counts.This insures a statistical accuracy of greater than 2%. Background should be subtracted from observed counts if it is statistically significant. The distance between the patient and the detector tube is important and must be maintained constant through immobilization of the head and neck.Obviously as the distance increases, errors produced by variations in thyroid depth decrease. Experience in working with a wide variety of scintillation equipment, as commercially available,leads us to believe that distance of 25-35 cm. (10-14 in.)between the source and the center of the sensitive volume of the tube or crystal is about optimal.If one actually uses two distances for each patient,accidental errors of distance measurement may be detected, and by the app li. cation of a simple formula,the depth of the active center of the thyroid estimated. (c) At this time any other Radio cap of that same lot,(their color coding system prevents face of the cube at the same point as the front of the patient ' sneck.This brings the capsule3.5cm. from the front face of the cube which approximates the average center of activity in the human thyroid.Illustration (6) The Phan to cube(R) is a carefully machined transparent cube of Plexiglass,6x6x9 cm. As the authors have shown (Nucleon ics,January 19551, it approaches quite closely the energy spectrum, and the actual observed " counts per mc.," of the usual cumbersome water phantom.This has been further checked by the use of full scale paraffin models ofthe human head and neck, where excellent agreement was observed.

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full yc a lib rated sterile solution of U.S.P. 1-131 containing exactly 25yc / c c as of filled with water and taken by the patient.The CUP must be well rinsed to in sure in - ges tion of the entire dose. behind a lead wall for subsequent use. Here i t is customary to maintain dosage relative - ly constant through the adjustment of the volume withdrawn,to care for radioactive decay, as in dLc ate don the chart accompanying each vial.A duplicate sample, measured in exactly the same way, is set aside in the standard bottle of the Phan to cube to act as the standard against which the thyroid is compared just as with the Radio cap.Illus - t ration (8). The activity involved in both cases is so small that no shielding of personnel is required, and washing s may be discarded in the hospital sewage system. The radiation emitted by the area of the patient " seen " by the detector consists of several components : (1) the direct.364 mev. primaries of the 1-131 plusa much smaller amount of the other energies of the spectrum as altered by. absorption of the tissues of the neck,(2) low energy gamma rays " reflected " and " scattered " by the skeleton and tissues of the neck and surrounding areas, and(3)similar radiations resulting from the iodide and thyroxine in circulation. (3) is normally small (2-390) at the end of 24 hrs., but(2) may represent some 20-30% of the observed radiation.Ifit is not eliminated or corrected for,the observed uptakes will be correspondingly erroneously high.This is a n error currently being made i n many laboratories. As Hine,etal,have shown, this secondary radiation may be largely eliminated by the use of a thin lead filter placed over the opening of the detector tube. Our data indicates that better than 90% of such secondaries are removed by a 1 / 32in.piece of lead with the simultaneous removal of only 10-2070 of the .364 mev. primaries.Since modern scintillation tubes give more counts than actually needed for accurate measurement of the usual tracer doses,this decrease is not of importance,especially when viewed in the light of the corresponding day.A dose is withdrawn from the " Tracer vial " with a suitable syringe This is transferred directly to a paper cup partially The syringe or Pipette is washed with H20 and put aside We have made repeated studies on the sensitivity of various detectors as supplied by the manufacturers. The distance between the sensitive volume of the tube and the san ple was in each instance 30 cm.,since this is now commonly employed. No filtration was used and backgrounds were determined in our counting laboratory using the shielding routinely supplied with the tube.

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14'' Na I Scintillation GOO - 900 matic correction for these two sources of error in thyroid measurements and permits direct inter comparison of the Radio cap or Tracer vial standard and the thyroid uptake. With less sensitive detectors,the use of this lead filter is not too practical, and reliance must be placed on the ability of the phantom alone,to simulate actual patient In order to secure the most favorable ratio Of true counts to background, and t o eliminate errors due to other sources of radiation in the area,the detector should have adequate lead shielding extending Well back ofthe crystal, and be provided with a vi ded can be of importance,especially if the area " seen " does not embrace all of the thyroid tissue area, or all of the Sample being measured. I t is our opinion that this collimator should be inthe form of acone,the exterior opening being not less than 11in.diameter, and the area of the Patient ' s neck covered by a circle of a t least 1 2 The weight of this shielding poses problems in the mounting of the tube, and the most versatile,and sometimes cheapest,solution at the moment, appears to be the modification of a n old X-Ray stand and flexible arm, permitting use with the patient in either an erect or a prone position.The Phan to cube and capsule likewise may be used in either position.Several commercial assemblies either place the scaler on a heavy cart, an integral part of which is a n arm for holding the detector,or mount the scaler on a modified X-Hay stand. One new detection arrangement designed for office and clinic use, with the patient erect, has the tube heavily shielded and mounted in a fixed position in the cabinet,which may likewise be placed on an office desk or a wheeled cart. In older work before the use of proper shielding and coll imation,it was customary to measure the " background " over the thigh,in an effort to simulate the activity in the blood and tissues of the neck.With present shielding, and with counts made at ad is - t ance from the neck,the ' lt high background, " has lost much of its older significance, except in severe hypo thyroid is m. Some groups prefer to place a 2-3 cm. thick lead disk immediately over the thyroid area and to take the counts then secured as "body backIn the absence of extensive metastases,this would seem t o be a very logical Direct inter comparison of any Radio cap from the same lot, (or a solution pipette dat the same time the dose was given), and the patient,eliminates the need for decay corrections. Simple division of the corrected counts per minute for the patient, by the counts per minute for the standard,under identical conditions,gives the apparent thyroid uptake. In general values greater than 45-50% Indicate hyperthyroidism,normal s usually show 15-45%, and hypo thyroids less than 10-1570 Physical considerations in any given counting system may shift the entire scale in either direction, and so each group should establish " normal " values for their particular setup. There are always " borderline cases , '* or instances where there is an obvious discrepancy between the uptake values and the clinical picture. Here there is obvious need for fur - the r data as determined by isotopic or other procedures.Certain of these will be discussed in subsequent sections. The time of 24 hours has been dictated by practical convenience as well as by wide clinical experience.In many cases i t is desirable to make measurements at intermediate times. Uptakes at less than4hours have sometimes been found to be erratic, and are