Khan M. Sajid  ( Pakistan Atomic Energy Medical Centre, Nishtar Medical College and Hospital, Multan. )
Sher M. Khan  ( Pakistan Atomic Energy Medical Centre, Nishtar Medical College and Hospital, Multan. )
Durr-e-Sabih  ( Pakistan Atomic Energy Medical Centre, Nishtar Medical College and Hospital, Multan. )
Fayyaz Ahmad  ( Pakistan Atomic Energy Medical Centre, Nishtar Medical College and Hospital, Multan. )

Technetium labelled Sucralphate has been used as an ulcer scanning agent in the gastrointestinal tract. The labelling described in the literature involves incubation of Tc99m-HSA (Human serum albumin) with Sucralphate. Due to difficulty in obtaining HSA we used bovine serum albumin (BSA) to tag radioac­tivity with Sucralphate.
The radioactive yields (Tagged Sucraiphate and Tc99m-BSA) obtained after purification were more than 99% pure and stable for several hours. Animal and human trials showed good localisation of the agent in ulcer bed (JPMA 38: 241, 1988).

Sucraiphate, a basic aluminium salt of sucrose octasuiphate’^1-2 a cytoprotective agent is used for the treatment of gastric and duodenal ulcer.
When taken orally it coats ulcerated areas due to strong electrostatic action between sucral­phate poly anions and proteins concentrated in ulcerated mucosa, which are positively charged. it thus provides a protective covering against acids enzymes and other irritants. This cytopro­tective barrier action lasts for as long as 6 hours^2-3
Technetium labelled sucraiphate may be used to visualise gastrointestinal ulcers⁴. Labelling involves mixing of the suspension of the agent in 0. IN HCI (pH4) with DTPA, HSA or fibrinogen already labelled with Tc99m or lyophilising a suspension of sucraiphate — DTPA — SnCl2 sucralphate—HSA--SnCI2, Sucralphate-fibrinogen SnCI2 with a saline solution of 99m Tc04⁵. Tc-99m-sucralphate-HSA — SnCl2 prepared using Tc99m—HSA has highest affinities for ulcerated areas and has been used by others^4-6-7 ,6 7 Due to non-availability of Tc99m—HSA we labelled bovine serum albumin (BSA) with Tc99m and used it to tag radioactivity to the drug. Methodo­logy, studies on normal human subjects and initial clinical data is presented.

1. Labelling of Sucraiphate in Vitro
Tc99m—HSA was prepared by first reduc­ing 5—lOmCi (200—400 MBq) pertechnetate (Tc04) with stannous chloride in acidic medium and then adding this mixture to 0.1% solution of BSA. The pH was then adjusted to 6 with dilute NaOH. The unreacted radioactivity was removed by passing the mixture through Dowax-l anion exchange resin (Tc99m-BSA appears in eluate and free 99m leO4 is retained by the resin)⁸.
200 MBq of Tc99m-BSA was added to 0.6 g powdered sucraiphate suspended in 0. IN HCI (pH4). The mixture was shaken, and then centri­fuged for ten minutes. The supernatant was removed, measured and discarded. The residue was resuspended in 5m1 of HCI (pH4) and centri­fuged, the supernatant discarded. The same proce­dure of washing was repeated twice and final yield of tagged sucralphate was measured.
Stability and Radiochemical purity of Tc99m-BSA was checked by paper chromato­graphy (Whatman No. 1 ,Acetone 90%: Water 10%). For checking stability, radiochromatograms of final yield of Tc99m-BSA were obtained at dif­ferent hours after preparation. Radiochemical purity of final yield of labelled sucraiphate was also checked by paper chromatography. The stability of tagged drug was checked by suspending the drug in HC1 solution at low pH (approxi­mately 1) and incubating the mixture in different tubes at 37°C for different time intervals. After each incubation the mixture was centrifuged and washed. Activity in the residue and supernatant was measured to assess bound and floating frac­tions.
The labelling yield of Tc99m-BSA obtained after purification by anion exchange chromatography was about 90% (X = 89.4 SD = 0.42 n = 10), whereas about 10% (X = 10.17 SD = 0.18 n = 10) activity was retained by the resin. Chromatographic results with purified Tc99m—BSA showed more than 99% of the label bound to the albumin (Xf - 0.65 SD = 0.02 n = 10) (Figure 1).

Labelled compound was found stable• until 5 hours without significant detach­ment of the radioactivity from radio yield (Figure 2 and Table. 1).


Radiochemical purity of tagged sucraiphate checked by washing procedure showed 98% of theadded activity bound to the drug (X 98.08 SD = 1.15 n 11), whereas paper chroma­tography showed more than 99% of the activity bound to the drug (Figure 3).

The tagged drug was found stable in low pH medium at 37°C with practically no floating activity. Results of washing the sucraiphate at different time intervals are
Animal studies using labelled sucraiphate(i)  Normal RabbitsTwo normal domestic rabbits were kept without food and water for 48 hours, followed by administration of 1 mCi (37MBq) of Tc99m-sucraiphate orally by a gastric tube. Serial analo­gue images were taken for upto 5 hours using a gamma camera. One picture was taken at 24 hours.
Animals were kept in specially designed portable cages with holes at the bottom for delivery of faeces. This was done to prevent the reingestion of faeces causing overestimation of stomach activity at 24 hours.
(ii) Rabbits with induced ulceration.
Two rabbtis kept without food and water for 48 hours received 600mg acetylesalicylic acid orally by a gastric tube. Eight hours later they received lmCi (MBq) of tagged sucraiphate. Serial analogue pictures were taken for 5 hours. One picture was taken at24 hours.

Animal Studies Normal Rabbits:
No area of focally increased activity in any of the rabbits was seen during the entire study. Clearance of radioactivity was however slow and diffuse images of stomach were obtained even after 3 hours of administration of labelled agent. No activity was detected outside GIT untill 4 hours of study. Slight radioactivity in the thyroid was seen after 4 hours. Activity was almost completely moved from stomach at 24 hours into the lower gut which was visualized.



Figures 4 & 5. Rabbits with induced ulcer. Focal areas of persistent activity (arrows) after stomachhas cleared TABLE II.

Bound activities of Tagged Sucraiphate deter­mined at various Time Intervals (at and after preparation) using washing procedure to fmd the stability of the Radiopharmaceutical.
2. Human Studies
Two males under 35 years of age with no history of GI disease volunteered for normal studies. After an overnight fast, they were given 0.5g of sucraiphate labelled with 3mCi of Tc99m-BSA. This was suspended in 200m1 of tap water and taken orally. 10 mg of metoclopramide syrup and a large drink of plain water was given after 30 minutes. This was done to hasten gastric emptying. Another large drink of plain water was given after one hour to wash residual activity from the stomach and duodenum. Anterior, right lateral, left lateral and posterior views were taken at 0, 0.5, 1, 1.5,2,2.5,3,4,5,24 and 48 hours respectively. The stomach, the small gut, the large gut were identified at 0 - 0.5, 2.5 and 3.5 hours respectively (Figure 6).



There was very little activity left in the stomach at 1 .5 hours. There was diffuse activity in the colon and rectum at 24 hours and no measurable activity at 48 hours.
Clinical trials were done in 37 cases of suspected peptic ulcer. All of them underwent either an upper G.l endoscopy⁹ (21 cases) or barium meal (5 cases) or both (11 cases). Eight cases were negative on enidoscopy or barium. Of 29 positive cases, 18 showed positive isotopic scanning, 9 were false negative and 2 scans were un-interpretable. On statistical analysis, the specificity of the test was 100%, sensitivity 76.3% and accuracy 80.4%.

Sucraiphate ulcer scanning has a good to excellent correlation with endoscopy for upper and lower GI ulceration. The method of prepara­tion is relatively easy and our experience with this compound has been very satisfying. There were initial difficulties in obtaining HSA in sufficient quantities from the local market therefore BSA was used instead of HSA. The radiochemical tests and early clinical experiences are convincing that the BSA linked compound isas effective as the frequently reported HSA linked agent. Studies in endoscopically confirmed cases of peptic ulcer showed good correlation of focally increased activity with abnormal areas reported on endos­copy⁹. Similar findings were observed in the present study.

The authors, are thankful to Mr. Akhtar Hussain for typing the manuscript, and to Prof. Shabbir A. Nasir and Dr. Mohammad Ali for referring endoscopically confirmed cases for
Sucraiphate scanning. An appreciation is also extended/o Mr. Akram Javed and Mr. Saifullah Khan for Gamma camera scanning and help in collection of data on normals and patients.

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