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JOURNAL OF NUCLEAR MEDICINE 7:807-816, 1966
Elimination of Liver Interference
from the Selenomethionine Pancreas Scan1
Ervin Kaplan, M.D., Moshe Ben-Porath, B.S., Sidney Fink, M.D.,
Glenn D. Clayton, B.S. and Burton Jacobson, M.D.
Hines, Illinois
Diagnosis of pancreatic disease by visualization of this organ has presented
many technical difficulties. The synthesis of 75Se selenomethionine has been a
major step in making possible the display of this organ by scanning techniques
(1, 2, 3, 4). The simultaneous localization of selenomethionine in the liver has
been a serious limiting factor in definition and delineation because the proximity
of the two organs may result in the liver anatomically overlying the pancreas.
Numerous attempts have been made to partially resolve this interference. These
methods include shielding the liver with lead (5); increasing the pancreatic
uptake with pancreozymin (6) and amino acids (7); retaining the pancreatic
secretions by constricting the sphincter of Oddi with morphine (8); and de
creasing the volume of secretion without altering uptake through use of pro
pantheline bromide (Probanthine) (7).
The capacity of the liver to concentrate gamma-emitting isotopes not con
centrated by the pancreas has been used to separately scan the liver. The limits
of this organ are then determined by superimposing the liver scan upon the
combined liver and pancreas scan obtained by conventional T5Se selenomethio
nine scanning (9). While the limits of the liver are defined by this method, the
limits of the pancreas are not.
The use of two channel pulse height analyzer systems has been proposed.
Initial studies of °5Znand 1311Rose Bengal were not successful (10). Computer
derived iso-response figures using a liver-seeking isotope and 75Se selenomethio
nine has been reported in a model system using a two-channel device (11). A
similar system has been reported by Spencer (12), but has not to our knowledge
been applied to the pancreatic scanning problem.
1From the Radioisotope and Medical Services, Veterans Administration Hospital, Hines,
Illinois, and the Departments of Medicine, University of Illinois College of Medicine and Loyola
University, Stritch School of Medicine.
807
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JOURNAL OF NUCLEAR MEDICINE 7:807-816, 1966

Elimination of Liver Interference

from the Selenomethionine Pancreas Scan

Ervin Kaplan, M.D., Moshe Ben-Porath, B.S., Sidney Fink, M.D., Glenn D. Clayton, B.S. and Burton Jacobson, M.D.

Hines, Illinois

Diagnosis of pancreatic disease by visualization of this organ has presented

many technical difficulties. The synthesis of 75Se selenomethionine has been a

major step in making possible the display of this organ by scanning techniques (1, 2, 3, 4). The simultaneous localization of selenomethionine in the liver has been a serious limiting factor in definition and delineation because the proximity of the two organs may result in the liver anatomically overlying the pancreas. Numerous attempts have been made to partially resolve this interference. These methods include shielding the liver with lead (5); increasing the pancreatic uptake with pancreozymin (6) and amino acids (7); retaining the pancreatic secretions by constricting the sphincter of Oddi with morphine (8); and de creasing the volume of secretion without altering uptake through use of pro

pantheline bromide (Probanthine) (7).

The capacity of the liver to concentrate gamma-emitting isotopes not con centrated by the pancreas has been used to separately scan the liver. The limits of this organ are then determined by superimposing the liver scan upon the combined liver and pancreas scan obtained by conventional T5Se selenomethio nine scanning (9). While the limits of the liver are defined by this method, the limits of the pancreas are not. The use of two channel pulse height analyzer systems has been proposed. Initial studies of °5Znand 1311Rose Bengal were not successful (10). Computer derived iso-response figures using a liver-seeking isotope and 75Se selenomethio nine has been reported in a model system using a two-channel device (11). A similar system has been reported by Spencer (12), but has not to our knowledge

been applied to the pancreatic scanning problem.

1From the Radioisotope and Medical Services, Veterans Administration Hospital, Hines, Illinois, and the Departments of Medicine, University of Illinois College of Medicine and Loyola University, Stritch School of Medicine.

807

808 KAPLAN,BEN-PORATH,FINK, CLAYTON,JACOBSON

Adaptation of conventional scanning equipment and a commercially avail able dual channel pulse height analyzer, countrate system has been made for the purpose of eliminating the liver image from the pancreatic scan. This system is described below, as well as the results obtained in scanning a model system and the pancreas in human subjects (13).

METHOD AND EQUIPMENT The patient is injected intravenously with both labeled selenomethionine and colloidal ‘9MAuas described below. The selenomethionine is concentrated in the liver and pancreas, the gold in only the liver. Predicated upon this differential distribution, the three or five-inch NaI( Tl) detector of a commercial scinti scanner' equipped with a five-inch focal length focusing collimator is placed over the right lobe of the liver remote from the pancreas. As described in the block diagram, Figure 1, the output of the detector is coupled to a dual channel pulse height analyzer, countrate meter system. One channel detects the 411 key ‘98Auphotopeak, the other simultaneously detects the 280 key 75Se photopeak, each through a 100 key window. The output of the two analyzers is coupled to two countrate meters. The 1@Au and the T5Se counts are separately observed. The countrates are balanced to be equal. The 198Au output is placed in a sub tract mode, and the two outputs are coupled through a DC to frequency con verter, Figure 2, to the input of the scanner. The patients were prepared by one of the following methods:

METHOD ONE The patient is prepared by fasting overnight. Breakfast consists of 300 grams of gelatin dessert containing 4.5 grams of protein, which is fed because of its relatively low methionine content. In the presence of abundant other amino acids, selenomethionine concentration in the pancreas may be enhanced. Thirty min utes following this meal, the patient is administered 100 @Cof 198Au colloid by intravenous injection. Seventy-five minutes after breakfast, the patient received % to 3@grains of morphine sulfate, the dose depending upon the patient's weight and tolerance, to assure constriction of the Spincter of Oddi (14). Fifteen mg of propantheline bromide (Probanthine) are administered at this time to decrease the fluid volume of the pancreatic secretion (15). The two agents used simul taneously should prevent phenomena related to increased intraluminal pressure

in the pancreatic ducts (16), without altering selenomethionine accumulation.

METHOD TWO The patient received a regular breakfast followed in 30 minutes by 100 @tC of ‘98Aucolloid by intravenous injection. Common to the two methods, 90 minutes to 120 minutes after breakfast, the patient is placed supine with the detector over the right lobe of the liver. Two hundred and fifty microcuries of T5Se selenomethionine are administered intra

1Picker Magnascanner III or IV

810 KAPLAN,^ BEN-PORATH,^ FINK,^ CLAYTON,^ JACOBSON

termined upon a model system. The model pancreas was a plastic container filled

with 75 microcuries of 75Se solution, while the liver was represented by a Man nelli-type plastic container with a hollow center. This container was filled with a solution of 90 microcuries of 198Au and 90 microcunies of 75Se. The system was subsequently tested upon 25 male subjects subjected to the regimen and dosage above described. The pancreas was scanned serially after administration of the labeled selenomethionine for periods up to 30 hours. Fourteen patients have been subjected to three or more serial scans. The anatomical configuration has been noted in the scans studied. Comparison is

made with conventional pancreatic scanning.

Six patients with known pancreatic pathology have been scanned to this

time as a prelude to more intensive evaluation of pancreatic disease by scanning.

RESULTS The results of scanning the model system described above may be visualized in Figure three. The 75Se within the inner plastic bottle may be visualized clearly

when the ‘98Auand 75Se in the outer container are eliminated by subtracting

gold from selenium. In the 25 patients scanned, the pancreas was consistently visualized with

.

Fig. 3. (a) End on scan of T5Se activity in two concentric containers, visualizing T5Se gamma photo peak. (b) Scan of T5Se activity in two concentric containers, visualizing 75Se gamma photo peak. Lateral view. (c) End on scan of 75Se activity in two concentric con tainers, outer container neutralized by subtraction of 198Au activity from T5Se activity. (d) Scan of 75Se activity in two concentric containers, outer container neutralized by subtraction of 198Au activity from T5Se activity. Lateral view.

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SELENOMETHIONINE PANCREAS SCAN 811

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Fig. 4. Pancreatic scan by gold subtract method, showing progressive accumulation of 75Se activity at (a) 30 minutes (b) 2 hours 30 minutes (c) 4 hours 30 minutes, and (d) 6 hours 40 minutes following injection of 75Se seleonomethionine. The subject was a 49-year old male with normal pancreatic function.

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Fig. 5. Selenomethionine pancreas photoscan by gold subtract method from a 75-year. old male subject showing pistol.shape configuration.

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SELENOMETHIONINE PANCREAS SCAN^813

the exception of three patients early in the series, while technical improvement in the circuitry was still being made. Serial scanning indicated continuous accumulation of T5Se in the pancreas for periods up to seven hours following intravenous administration of labeled selenomethionine. This criteria for accumulation was successively denser pan creatic images with the maintenance of constant scanner control settings and patient-detector geometry (See Figure 4). Such accumulation was decreased by a regular lunch, but was not effected by substituting a glass of orange juice for lunch. The principal anatomical variations in the normal pancreas encountered in this study are exemplified by the pistol-shaped pancreas, (Figure 5); the pan creas with a large head and small tail, (Figure 6), and the most common variant encountered in this study in which the tail is more massive than the head and a marked attenuation is observed where the pancreas crosses the vertebrae, (Figure 7c). This latter figure also compares the ‘98Auliver scan (7a), the 75Se scan (7b) and the gold subtract scan which eliminates the liver (7c). Insufficient cases of carcinoma of the pancreas and chronic pancreatitis have been completed to make any significant evaluation of this technique in pancreatic pathology. Two illustrative scans are included to indicate our pre liminary findings in pancreatic disease. Figure 8 shows the pancreatic scan in carcinoma of the pancreas. The day following the scan, laparotomy demonstrated that this 59-year-old white male with obstructive jaundice had virtual destruction of the head of the pancreas and a portion of the tail by carcinoma. Figure 9 mdi

Fig. Th. A photoscan showing distribution of 75Se in the liver and pancreas of the sub ject in (a). Note the overlap of the two organs.

814 KAPLAN, BEN-PORATH, FINK, CLAYTON, JACOBSON

cates a scan obtained in a 42-year-old male with a history of chronic pancreatitis. The pancreas was visualized, but was markedly shrunken in size. Decreased size was not necessarily an observed characteristic in other patients with this diagnosis.

DISCUSSION The routine visualization of the normal pancreas without interference from the liver may now be accomplished using conventional three-inch and five-inch detectors and scanning systems with the subtract system described. The patient may be adequately prepared by eating a regular breakfast. The continuing ac cumulation of 75Se in the pancreas would suggest that the most appropriate time for the scan would be four hours following breakfast and two hours following the injection of labeled selenomethionine. The mechanism of continued accumu lation should be further investigated, as free selenomethionine has been re ported to disappear from the circulation in approximately 30 minutes and re appear as protein-bound 75Se activity (17). The mechanism of accumulation from the protein-bound moiety suggests, but certainly does not verify, incorpo ration of more complex molecules than amino acids by the pancreas. Use of the subtract technique for scanning can be accomplished with smaller dosage of 75Se and ‘98Authan was used in the current study. It is suggested that evaluation of pancreatic disease may be enhanced by this technique. Its applica tion in scanning other organs is indicated.

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Fig. 7c. A photoscan of the 75Se selenomethionine in the pancreas of the subject in (a) obtained using the gold subtract technique. Note the attenuation of the pancreas as it over lies the vertebrae.

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816 KAPLAN,BEN-PORATH,FINK, CLAYTON,JACOBSON

SUMMARY

A method of scanning the pancreas is described, in which the liver image

is eliminated by the subtraction of the radio gold photopeak from that of selenium-75. The electronic system is pictured in block and detailed circuit dia gram. The system has been useful in consistently producing a pancreatic image.

ACKNOWLEDGMENT We wish to acknowledge the cooperation in this study of Picker Nuclear Di vision of Picker X-Ray Corporation, and Dr. Paul Numerof of E. R. Squibb and Sons.

REFERENCRS

  1. KAPLAN,E., CLAYTON,C., FINK, S., JACOBSON,B. ANDBEN-PORATH,M. : Elimination of Liver Interference from the Selenomethionine Pancreas Scan; burn. Nuclear Med. 7:387,
  2. BIAu, M., MANCKE, R. F., AND BENDER, M. A.: Clinical Experience with Selenomethi onine for Pancreas Visualization. burn. Nuclear Med. 3:202, 1962.
  3. SODEE, D. B.: Radioisotope Scanning of the Pancreas with Selenomethionine (75Se), Radiology 83:910, 1964.
  4. Bi.Au, M., Pancreas Scannings with Se75 Selenomethionine, Medical Radioisotope Scanning 2:275 IAEA, Vienna, 1964.
  5. SODEE,D.B.: Radioisotope Scanning of the Pancreas with Selenomethionine Se75, Medical Radioisotope Scanning 2:289 IAEA, Vienna, 1964.
  6. HAYNIE, T. P., Sv0B0DA, K. C. AND ZUIDEMA, G. D.: Diagnosis of Pancreatic Disease by Photoscanning; Journ. Nuc. Med. 5:90-94, 1964.
  7. TABERN, D. L., KEARNEY,J. AND DOLBOW,A.: The Use of Intravenous Amino Acids in the Visualization of the Pancreas with Seleno 75 Methionine; Journ. Nuclear Med. 6:762- 766, 1965.
  8. RODRIGUEZ, ANTUNEZ, A.: The Use of Morphine in Pancreatic Scanning with 75Se Methionine. Journ. Nuclear Med. 5:729, 1964.
  9. BURDINE, J. A. AND HAYNIE, T. P.: Diagnosis of Pancreatic Carcinoma by Photoscan fling;Journ.AMA 979-981,1965.
  10. ARONOW, S., THORS, R. AND C. L. BROWNELL: Positron Scanning of Liver and Pan creas, Medical Radioisotope Scanning 105, IAEA, Vienna, 1959. BENDER, M. A.: ibid 123.
  11. SCHEPERS, H. AND WINKLER, C.: An Automatic Scanning System Using A Tape Perforator and Computer Technique, Medical Radioisotope Scanning 1:321 IAEA, Vienna,
  12. SPENCER,R. P.. Simultaneous Use of Two Radioisotopes by Scanner Plus Analogue Computer Coupling, Journ. Nuclear Med. 6:844, 1965.
  13. BErc-P0RAm, M., CLAYTON, C. AND KAPLAN, E.: Selective Visualization of the Pancreas my a Subtractive Double Radioisotope Scanning Technique. Trans. of the American Nuclear Soc. 9 (In Press) 1966.
  14. BUTSCH, @V.C., MCGOWAN, J. M., AND WALTERS, W. W.: Clinical Studies on the Influence of Certain Drugs in Relation to Biliary Pain and to the Variations in Intrabiliary Pressure. Surg. Gynec. & Obst. 63:451-456, 1938.
  15. THoMAs, J. E.: Mechanism of Action of Pancreatic Stimuli Studied by Means of Atropine-like Drugs. Am. J. Physiol. 206:124-128, 1964.
  16. SANGSTER, A. J.: The Uses of Morphine and Propantheline in Intravenous Cholecyst ography. Lancet. 2:525-527, 1955.
  17. OLDENDORF, \V. H. AND KITANO, M.: Selenomethionine Reappearance in Blood Fol lowing Intravenous Injection, Journ. Nuc. Med. 4:231, 1963.