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 hours2-3
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 others4-6-7 ,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.
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.
1. Morikawa, H. et al. Structural analysis of amorphous sodium salt and aluminium hydroxide salt sucrose sulphate. j. Chem. Soc. Farady Trans., 1981; 1,77:629.
2. Nagashima, R. and Yoshia, N. Sucralfate, a basicaluminium salt of sucrose sulfate. 1. Behaviours in gastroduodenal pH. Arzneimittelforsch:, 1979; 29:1668.
3. Nagashima, R. Mechanisms of actions of sucralfate. J. Clin. Gastroenterol., 1981; 3 (Suppl. 2): 117.
4. Vasquez, T.E., Bridges, R.L., Braunstein, P., Jansholt, A.L. and Meshkinpour, H. Work in progress. Gastrointestinal ulcerations; detection using a technetium-99m labelled ulcer-avid agent. Radiology, 1983; 148:227
5. Gill, M.C., Godoy, N., Mena, P., Sole, C. and Munoz, J. Marcacion de Tc99m-surcralphato y su evaluacion Ia deteccion de ulcera gastroduodenal.IAEA 45/30.,1984:273-279.
6. McHardy, G.G. A multicentre, double-blind trial of sucralfate and placebo in duodenal ulcer. J. Din. Gastroenterol., 1981 ;3 :147.
7. Dawson, 3D., Khan, NA., Nuttal, P. and Shreeve, R.D. Technetium-99m labelled sucralphate isotope scanning in detection of peptic ulcerations. Nuclear Med. Communications, 1985; 6: 319.
8. Saha B. Gopal. Fundamental of nuclear pharmacy.2nd ed. New York, Springer-Verlay, New York, p.105
9. Tedesco, FJ. Endoscopy in the evaluation of patients with upper gastrointestinal symptoms; indications, expectations and interpretation. J. Clin. Gastroenterol., 1981; 3 (Suppl. 2) : 67.