The use of 99mtechnetium pertechnetate to detect transplanted gastric mucosa in the dog

The Use of “Technetium Pertechnetate to Detect Transplanted Gastric Mucosa in the Dog By Cedric J. Priebe, Jr., David

S. Marsden,

and Bozidar

Lazarevic

I

N 1962, WHEN HARPER, ANDROS, AND LATHROP’ reported the advantages of 99mtechnetium pertechnetate as a biologic tracer material, they stressed its short half-life of 6 hr, the near absence of particle radiation, and the low energy (140 keV) of its principal gamma ray, all of which made it ideal for scanning techniques. They found that about 25% of the 99mT~injected dose localized in the stomach and suggested that “the diagnosis of a Meckel’s diverticulum containing gastric mucosa should be possible.” Gastric scanning in humans was initially pursued overseas2A and then in the United States by Marsden et al.s It was not until 1970 that Jewett, Duszynski, and Allen6 first described two children with rectal bleeding due to a Meckel’s diverticulum who had a preoperative 99mT~scan showing an area of abnormal uptake. Since this original report, ten additional patients’-” with a positive scan for ectopic gastric mucosa in a Meckel’s diverticulum have been described with pathologic confirmation. In the clinical setting we, as did others,’ noted the inconsistency of the 99mT~ scan in localizing ectopic gastric mucosa. To better understand this scanning technique and its deficiencies, surgical models of a Meckel’s diverticulum with ectopic gastric mucosa were constructed in the dog. 99”Tc scans were performed, and the specimens were later studied by radioactive uptake counts and radioautographs. Our objectives were (1) to study the reliability of scintiphotography in detecting ectopic gastric mucosa, (2) to determine the smallest amount of gastric mucosa that could be identified, (3) to localize the site of 99mT~uptake in the model, and (4) to note if an area of healing intestinal surgery would produce a positive scan. MATERIALS

AND

METHODS

Seven mature mongrel dogs weighing 11-22 kg, treated with appropriate immunizations and vermifuges, were anesthetized with sodium pentobarbital and subjected to laparotomy. In each dog a full-thickness patch of stomach wall from the midportion of the greater curvature, utilizing the left gastroepiploic vessels as a vascular pedicle, was implanted into the open end of a Roux-en-Y ileoileostomy (Fig. 1). The gastric patches varied in size from 3 x 2 cm to 2 x I cm and were marked with several metal sutures for radiographic localization. The ileal spur was between 5 and 10 cm long and was located 5-10 cm from the ileocecal valve. All animals withstood the procedure well and began taking a standard kennel diet after several days of intravenous fluids.

From the Departments of Surgery (Pediatric Surgery Service), Radiology and Pathology, The Roosevelt Hospital, and the College of Physicians and Surgeons, Columbia University, New York, N. Y. Presented before the Fifth Annual Meeting of the American Pediatric Surgical Association, New Orleans, La, April 4-6, 1974. Supported in part by USPHS Grant S-SOI-RR-056663-06. Address for reprint requests: Cedric J. Priebe, Jr., M.D.. The Roosevelt Hospital, 428 W. 59th St., New York, N. Y. 10019. 0 1974 by Grune & Stratton, Inc. Journal of Pediatric Surgery, Vol. 9, No. 5 (October), 1974

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’

Schematic drawing

of surgical

model of

All scans were performed with a Nuclear Chicago gamma camera using a 4000-hole technetium collimator while the fasting animal was anesthetized. Scintiphotographs were taken 15-180 min after the intravenous injection of I-10 mCi of WmT~. Scanning was done in the anterior and lateral positions. Each dog had a control scan before the surgical model was constructed and then two to four subsequent scans from I wk to I4 mo later. In two dogs, a final scan was done 4 days or 14 days after excision of the surgical model. The Meckel’s models were excised 3-18 mo after construction, I hr after the intravenous injection of 10 mCi of 99mTc. The intestine was opened and the ectopic gastric mucosa measured to obtain its approximate surface area (Fig. 2). The concentration of WmTc in the gastric and ileal mucosa was measured in a well scintillation counter. Fifty-two contact radioautographs were made by exposing dental films for 2 or 3 days to frozen sections of the excised full-thickness

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Fig. 3. Scintiphotogrophs from dog 2. (A) Control scan, anterior view, 145 min after 10 mCi scan, onterior view, 70 wmT~. (Et) Postoperative min after 10 mCi wmTc, showing ectopic Oreo of increased uptake. (C) Scan otter excision of Meckei’s model, anterior view, 100 min after 6.3 mCi wmTc, showing absence of Oreo of ectopic uptoke.

gastric and ileal tissue. These frozen sections were then stained comparison with the radioautographs. This method of contact previously to study the stomach after 99mTc scans.‘2313

with hematoxylin radioautography

and eosin for has been used

RESULTS

The abdominal scintiphotographs showed increased uptake of 99mTc in the stomach and urinary bladder in all dogs. Areas of increased background were also seen in some animals especially overlying the duodenum and upper jejunum. An additional distinct area of increased uptake was consistently present on 14 scans in five dogs after formation of the Meckel’s mode1 (Fig. 3). Best definition was seen 45 min after WmT~injection and then remained for 3 hr. It was noted that the dimensions and approximate surface area of the excised gastric mucosa varied somewhat from those when it Gas constructed (Table 1). This was most likely due to the effects of suture approximation and anastomotic healing. All five models that had a consistently positive *“‘Tc scan had 1.8 sq cm or more of ectopic mucosa. Abdominal roentgenograms identifying the metallic marking sutures in the ectopic gastric mucosa correlated well with the site of the ectopic uptake seen on the scans. The scans during the 2 wk after excision of the models in two dogs showed an absence of the previous area of increased uptake (negative scan). Table 1. wmTc Scintiphotogrophy

Constructed Qog

Gastric

for Ectopic Gastric Mucoso Surface

Size of Timer

Patch

Studied

Results Each

of

Study’

Area

of Excised Gastric

Mucoso

Gastric/lb.4 WmTc

Countr/100 Mucosa

1

3.0 x 2.0 cm

4

++i+

6.8 cm2

15/l

2

3.0 x 2.0 cm

3

+++

5.0 cm2

611 13/l

3

2.0 x 2.0cm

3

+++

5.0 cm2

4

2.5 x 2.0 cm

2

++

2.2 cm2

13/l

5

2.5 X 2.0 cm

2

++

1.8 cm2

6

2.0 x 1.5 cm

4

1.5 cm2

8/l 20/l

7

2.0 x 1.0 cm

2

1.3 cm2

tet

*+

= visualization;

tte

= technical

error.

-

= nonvisualizotion.

mg

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Fig. 4. (A) Throw nriol sections of the surgical modal in dog I; (6) cormsponding contact radioautograph. Ectopic gastric mucosa lies to the loft of tho arrow, iloal mucosa to tho right. in tho surface of tho gastric mucosa Tho radioautograph domonstmtos concontmtion of *Tc but only minimal to absont uptako in tho iloal mucosa. Homatoxylin and losin, macrophotograph.

Radioactivity counts demonstrated that the ectopic gastric mucosa had 6 to 20 times the count rate of the ileal mucosa per 100 mg. The contact radioautographs were compared with the hematoxylin and eosin-stained sections from which they were made. All seven dogs demonstrated concentration of radioactive 99mTc in the mucous cells of the gastric mucosal surface and gastric pits (Fig 4, 5A and 5B). Radioactivity concentration was not seen over the gastric glands, which contain the chief, parietal, and neck cells. DISCUSSION

Accurate diagnosis of serious painless rectal bleeding in infants and children remains difficult. Barium contrast studies are usually unrewarding. Selective mesenteric arteriograms have proved helpful during an active bleeding episode in adults and older childreni but this invasive procedure presents technical problems in small children. Shandlingls has reported that 40% of 61 young children with previously undiagnosed rectal bleeding had a Meckel’s diverticulum at laparotomy. It has been found that ectopic gastric mucosa is present in 90%i6 to 97%” of such bleeding Meckel’s diverticula. A method of detecting this ectopic gastric mucosa as well as that in intestinal duplication.@ would have good clinical applicability. The 99mT~gastric scan theoretically appeared to fill this need, but, unfortunately, it has not been reliable in clinical use. In our experimental study in the dog, injection of l-10 mCi of 99mT~produced scans of good quality. Scintiphotographs on Polaroid film obtained with a gamma camera offered a more simple and rapid technique than rectilinear scanning. The best clarity of areas of ectopic gastric mucosal uptake were ob-

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Fig. 5. (A) Ectopic gastric mucosa in dog 1. Photomicrogmph demonrtmting mucous collr along the rurfaco and gastric pits, the muscularis mucosa at the bottom, and the gastric glands in botwoon. Homatoxylin and -sin, original magnification x 35. (8) Contoct radioautagmph of this ama showing ponrlc concontmtod in the gastric mucous collr of the surface and gastric pits. Original magnification x 35.

tained 45-60 min after g9mT~ injection. Longer time intervals offered no improvement in scan information. The effect of gastric secretions passing down the intestinal tract was minimized by fasting the animal. However, in some dogs diffuse areas of increased uptake were seen, usually after several hours, especially .overlying the duodenum. This was felt to be due to the passage of radioactive secretions out of the stomach into the small intestine.

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Areasof ectopic gastric mucosa were consistently identified if they were larger than 1.8 sq cm. Smaller patches were not seen against the general background of radioactivity in the blood, intestine, and urinary tract even though the direct radioactive counts and radioautographs showed increased uptake in the specimens. The resolution capability of the scanning equipment influenced our ability to visualize such small areas. Thus, the size of the area of ectopic uptake appeared critical. The ability of the gastric scan to experimentally demonstrate relatively small areas of gastric mucosa has also been noted by Safaie-Shirazi et a1.,i9 who were able to identify l-cm retained antral cuffs after gastrectomies in dogs. One might estimate that this represented 3-5 sq cm of gastric mucosa. The cellular location of 99mTc in gastric mucosa has been studied by various radioautographic techniques. Meier-Ruge and Fridrich*O after study in three cats and two humans stated that WmT~was selectively secreted by the parietal cells. In contrast, Marsden et al. ‘*J have shown that in dogs it is concentrated by the mucus-secreting cells of the gastric mucosa in a similar fashion to the concentration of i3’I.*’ The radioautographs of the ectopic gastric tissue in our Meckel’s mode1 also showed that 99mT~was concentrated in mucous cells of the gastric mucosal surface and gastric pits, but not in the parietal or chief cells of the stomach or in the mucosa of the ileum. Attempts to stimulate gastric mucus production with histalog,** unfortunately, have not increased the visualization of the ectopic gastric mucosa in other studies.23 In clinical use we were unable to visualize 4 sq cm of ectopic gastric mucosa in a Meckel’s diverticulum in a 3-yr-old boy with a history of rectal bleeding. This occurred in spite of an increased radioactive count in the gastric mucosa of the excised specimen after 99mTcinjection. The negative scan may have been due to blurring of the image due to movement of an awake child or to the greater radioactive background in the human, who has more intestinal length and abdominal bulk than the dog. Rosenthal1 et al.’ were also unable to demonstrate areas of increased uptake in four of eight children with ectopic gastric mucosa in Meckel’s diverticula. A negative scan thus does not rule out the presence of a small amount of ectopic gastric mucosa. The critical amount necessary for visualization in humans may be larger than the 1.8 sq cm seen in our dog experiments, Pretreatment of patients with perchlorate before WmT~ brain scanning” was originally suggested to decrease uptake by the choroid plexus, thyroid, and salivary glands. Perchlorate also has been used by several authors6*8,1’*25 before scanning for ectopic gastric mucosa, contrary to the advice of others’T3*4*26 who showed that it decreased 99mTcgastric uptake. In other experiments in dogs we23 have demonstrated a similar decrease in uptake and even a washout of 99mTc from gastric mucosa after perchlorate administration. Although treatment with perchlorate is contraindicated before scanning for gastric mucosa, its use after completion of the scan to increase the rapidity of elimination of WmT~ may have merit4 In this way, the low radiation dose of 100-300 mrad to the patient could be further reduced. False positive scans for ectopic gastric mucosa have been noted clinically by Duszynski et al.*’ m . jejunal intussusception, intestinal obstruction, and after

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the ingestion of gastrointestinal irritating drugs. The jejunal intussusceptions were felt to visualize due to venous congestion and interstitial edema. It is interesting that Rosenthal et al.’ noted negative scans in two children with ileocolic intussusceptions. Our inability to detect an area of postoperative vascular congestion and inflammation at the site of a healing intestinal anastomosis is noteworthy. An increase in gastrointestinal secretions or pooling of secretions behind an intestinal obstruction could certainly explain some false positive scans. Chaundhuri et a1.2*described a misleading positive scan in an adult who had only a tiny 3 x 4-mm telangiectatic jejunal vascular lesion. They called attention to the possibility of obstructive urinary tract lesions causing more proximal areas of increased uptake. Thus, an ectopic area of increased uptake in a gastric scan does not necessarily indicate the presence of ectopic gastric mucosa. Although false negative and false positive 99mT~ scans for ectopic gastric mucosa do occur, the study should be done in children who have significant painless rectal bleeding, or chronic abdominal pain, or a mass of obscure etiology. Scanning should be performed before any barium contrast studies, as overlying barium will absorb radioactive energy and prevent visualization of areas of ectopic uptake. The 99mTc scan will be most helpful when it is positive and is evaluated in conjunction with the clinical picture. Such a positive scan in a fasting child with a history of recta1 bleeding should be a strong indication for a laparotomy for a suspected Meckel’s diverticulum or a communicating duplication. However, a negative scan in the same type of patient should not mitigate against an operation if other factors suggest it. It should also be noted that identification of 99mTc in gastric mucosa located in the chest has proved of value in the diagnosis of mediastinal enteric cysts,29 hiatus hernia,29 and Barrett’s esophagusN SUMMARY

A surgical model of a Meckel’s diverticulum with ectopic gastric mucosa was constructed in seven dogs by implanting a full-thickness patch of gastric wall into the open end of a Roux-en-Y ileoileostomy. 99mT~ Pertechnetate scintiphotography with a gamma camera consistently identified this ectopic gastric mucosa when it was 1.8 sq cm or larger. Excision of the surgical models after WmT~injection showed that gastric mucosal radioactive counts were 6-20 times those in the adjacent ileum. Contact radioautographs of the specimens compared to the histologic sections from which they were made demonstrated that the 99mTc was concentrated in the mucous cells of the gastric mucosal surface and gastric pits. 99mTc Scintiphotography should be utilized to identify ectopic gastric mucosa in symptomatic patients, recognizing that the amount of ectopic gastric mucosa present will be one determining factor in visualization. REFERENCES 1. Harper PV, Andros G, Lathrop K: Preliminary observations on the use of six-hour Tc 99m as a tracer in biology and medicine. Argonne Cancer Research Hospital Semiannual

Report to the Atomic Energy Commission, No 18, Office of Technical Service, Department of Commerce, Washington 25, DC, 1962 2. Harden RMcG, Alexander WD, Kennedy

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I: Isotope uptake and scanning of the stomach in man with 99mTc-pertechnetate. Lancet 1:1305, 1967 3. Hofmeyr NG: Stomach scanning after intravenous 99mTc administration. A preliminary report. S Afr Med J 41:572, 1967 4. Mikolajkow A, Chomicki OA: Scanning of the stomach with 99mTc. Digestion 3:357, 1970 5. Marsden DS, Alexander CH, Yeung PK, et al: The use of 99mT~ to detect gastric malignancy. Am J Gastroenterol59:410, 1973 6. Jewett TC, Duszynski DO, Allen JE: The visualization of Meckel’s diverticulum with 99mTc-pertechnetate. Surgery 68:567, 1970 7. Rosenthal1 L, Henry JN. Murphy DA, et al: Radiopertechnetate imaging of the Meckel’s diverticulum. Radiology 105:371, 1972 8. Kilpatrick ZM, Aseron CA: Radioisotope detection of Meckel’s diverticulum causing acute rectal hemorrhage. N Engl J Med 287: 653, 1972 9. Jaros R, Schussheim A, Levy LM: Preoperative diagnosis of bleeding Meckel’s diverticulum utilizing 99mtechnetium pertechnetate scinti-imaging. J Pediatr 82:45, 1973 10. Berquist TH, Nolan NC, Adson MA, et al: Diagnosis of Meckel’s diverticulum by radioisotope scanning. Mayo Clin Proc 48:98, 1973 11. Keramidas DC, Voyatzis N: Radioisotope diagnosis of a Meckel’s diverticulum causing intestinal bleeding. Z Kinderchir 13:210, 1973 12. Marsden DS, Alexander CH, Yeung P, et al: Autoradiographic explanation for the uses of 99mTc in gastric scintiphotography. J Nucl Med 14:632,1973 13. Marsden DS, Lazarevic B, Alexander C: Gastric location of ‘?odide and 99mtechnetium pertechnetate and its clinical implications. To be published. 14. Nusbaum M, Baum S, Blakemore WS: Clinical experience with the diagnosis and management of gastrointestinal hemorrhage by selective mesenteric catheterization. Ann Surg 170:506, 1969 15. Shandling, B: Laparotomy for rectal ‘bleeding. Pediatrics 35:787, 1965 16. Benson CD: Surgical implications of Meckel’s diverticulum, in Mustard WT, Ravitch MM, Snyder WH Jr (eds): Pediatric Surgery, Chicago, Year Book, 1969, p 864 17. Rutherford RB, Akers DR: Meckel’s diverticulum: A review of 148 pediatric pa-

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tients, with special reference to the pattern of bleeding and to mesodiverticular vascular bands. Surgery 59:618, 1966 18. Mellish RWP, Koop CE: Clinical manifestations of duplications of the bowel. Pediatrics 27:397, 1961 19. Safaie-Shirazi S, Chaundhuri TK, Chaundhuri TK, et al: Visualization of isolated retained antrum by using technetium-99m Surgery 73~278, 1973 20. Meier-Ruge W, Fridrich R: Die Verteilung von Technetium-99m und Jod- 13I in der Magenschleimhaut. Ein Beitrag zur Methodik der Mikrohistoautoradiographie wasserltislicher Isotope. Distribution of technetium-99m and iodine-131 in the gastric mucosa. A technique to determine microhistoautoradiographical distribution of water soluble isotopes. Histochemie 19:147, 1969 21. Logothetopoulos JH, Myant NB: Concentration of radio-iodide and 35S-labelled thiocyanate by the stomach of the hamster. J Physiol 133:213, 1956 22. Wise L, Ballinger II WF: The effect of histalog on canine gastric acid, mucus and pepsin secretion. Ann Surg 171:229, 1970 23. Marsden DS, Priebe CJ Jr: Preliminary appraisal of present 99mT~ techniques for detecting ectopic gastric mucosa. To be published. 24. Oldendorf WH, Sisson WB, Iisaka Y: Compartmental redistribution of 99mTcpertechnetaie in the presence of perchlorate ion and its relation to plasma protein binding. J Nucl Med 11:85, 1970 25. White AF, Oh KS, Weber AL, et al: Radiologic manifestations of Meckel’s diverticulum. Am J Roentgen01 Radium Ther Nucl Med 118:86, 1973 26. Smith EM: Internal dose calculation for 99mT~.J Nucl Med 6:231, 1965 27. Duszynski DO, Jewett TC, Allen JE: Tcaam Na pertechnetate scanning of the abdomen with particular reference to small bowel pathology. Am J Roentgen01 Radium Ther Nucl Med 113:258, 1971 28. Chaundhuri TK, Chaundhuri TK, Christie JH: False positive Meckel’s diverticulum scan. Surgery 71:313, 1972 29. Mark R, Young L, Ferguson C, et al: Diagnosis of an intrathoracic gastrogenic cyst using 99mTc-pertechnetate. Radiology 109: 137, 1973 30. Berquist TH, Nolan HG, Carbon HC, et al: Diagnosis of Barrett’s esophagus by pertechnetate scintigraphy. Mayo Clin Proc 48:276, 1973