ucralfate, the basic aluminum salt of sucrose octasulfate (Fig. 1) is used in the treatment of peptic ulcers.Sucralfate binds to the ulcerated surface by chemicallycomplexing with the exposed protein. Since the molecule has a high molecular weight and has eight potentially hydrolyzable alumina groups, it protects the ulcerated surface from contact with the stomach acid andpepsin, thus reducing the immediate discomfort andfacilitating the healing process.

Vasquez et al. (1) conceived the idea that the naturalaffinity ofsucralfate for proteins could be used to attacha radioactive marker to the sucralfate. Provided thesucralfate molecule retained its ability to bind proteinsafter the radiolabeled protein is attached to it, it wouldthen be possible to use this sucralfate labeled proteincomplex to localize and image peptic ulcers. In theirfirst clinical report ofthis technique, Vasquez et al. (1)used technetium-99rn-labeled human serum albumin([@Tc]HSA) to complex with sucralfate ([@Tc]HSAsucralfate). They were able to image ulcers in theirpatients following oral administration of the resultantcomplex. Since that time, there have been a number ofliterature reports of the use of labeled sucralfate in theclinical imaging ofgastric and duodenal ulcers (2) andinflammatory bowel disease (3). In 1985 Pera et al. (4)reported a direct in vivo technique for labeling sucralfate in the detection of gastric ulcers. This technique

ReceivedJune 27, 1988;revision accepted Nov. 8, 1988.Forreprintscontact:MW.Bilhinghurst,Ph.D.,HealthSciences

Centre,700WilliamAve.,Winnipeg,Manitoba,Canada.

involved the oral administration of a sucralfate/stannous ion suspension followed 2 hr later by oral administration ofpertechnetate. In developing this technique,Pera et al. (4) demonstrated that sucralfate could bedirectly labeled with @TcO4in the presence of stannous ion. In 1987, Vasquez et al. (5) reviewed theclinical uses of @“Tc-labeledsucralfate, however, thereis still very little data available on the chemical natureand stability of the bond between @Tcand the localizing entity, sucralfate. It is known (6) that the affinityof sucrose octasulfate for albumin drops off rapidly ata pH above 4. Since sucralfateis a basic aluminum saltof sucrose octasulfate, there is reason to be concernedthat at a high pH, such as that encountered in theduodenum and ileum, the albumin sucralfatecomplexmay not exhibit very good stability. Thus, a loss of theradioactive marker, i.e., the [@“Tc]HSA,might occurwhen the [@mTc]HSA@sucralfateis used to localize duodenal ulcers or inflammatory bowel disease. Since theattachment of the [@TcJHSA and the localization ofthe sucralfate to the denuded mucosa share the samebinding site on the sucralfate molecule, the possibilitythat labeling ofsucralfate with [@“Tc]HSAmay reducethe affinity of sucralfate for the site of biological localizalion must be considered.

This current work represents an in vitro study of thecharacteristics of @Tc-labeledsucralfate. Factors sf.feeling the labeling and stability of both [@mTc]HSA@sucralfate and directly labeled sucralfate ([@“Tc]sucralfate) have been investigated.

523Volume30 •Number4 •April1989

Chemical Aspects of Labeling Sucralfatewith 9@TcO4Mervyn W. Billinghurst, Douglas N. Abrams, and Margaret S. Lawson

Radiopharmacy, Health Sciences Centre, Winnipeg, Manitoba

Twoformulationsof [@Tc]sueraIfatehavebeenusedto imagegastricandduodenalulcersand inflammatory bowel disease. One formulation is a complexation of [@‘Tc]HSAwithsucralfate. The second is prepared by directly labeling sucralfate with [@“TcJpertechnetateinthe presence of stannous ion. An in vitro study of the factors affecting the production andsta@Iityof these labelad sucraifate preparations was conducted. Both formulations werestableat the acidicpH likelyencounteredin the stomach.However,at pH> 6 the albuminsucralfate complex began to dissociate while directly labeled sucralfate was stable to a pH of9. Converselyit was shownthat directlylabeledsucralfatewas moresusceptibleto lossof

@Tcto other chelating species. Sucraifate complexed with [@FcJHSA was radiOchemiCaltystable up to a specific actMty of 26 GBq (700 mCi) per gram while directly labeled sucralfateshowed decreased 24-hr stabilityat specific activffies>837 mCi (31 GBq)per gram.

J NucIMed 30:523—530,1989

micron (25 mm diameter) disposable filter unit (MSI). Thisaliquot was then washedthroughthe filterwith 2 ml of saline.

The ifiterand the filtratewere countedseparatelyon asodium iodide crystal coupled to a pulse height analyzer setfor @mTc.The labelingefficiency was calculated as follows:

. . counts on filter

labeling efficiency = .counts on ifiter + counts in filtrate

Optimization of @@@TcJHSA@SucraIfatePreparationEffectoftime ofincubation.After the additionofthe [@mTcJ

HSAto thesucralfate,thesuspensionwasrotatedforvarioustime intervals (5, 10, 15, and 30 mm). The suspension wassampled and the labeling efficiency was determined.

EffectofpH. The pH of the 10 ml of diluted [@Tc]HSAsolutionwas controlledby adjustingthe pH of the diluentwith either 0. iN HCI or 0. iN NaOH. The appropriately pHadjusted diluent (8.6 ml) was added to 1.4 ml of [@“Tc]HSApriorto addition of sucralfatepowder.

Effectofstannous ion concentrationonf@mTc]HSA@sucral@fate binding. A stock solution of stannous chloride was prepared by dissolving0.5 g oftin metal in 4 ml of concentratedHQ. Uponcompletedissolution,thevolumewasmadeupto50 ml with physiological saline, filteredthrough a 0.2-micronifiter (MSI) into sterile multidose vials. The vials were thenflushedwithnitrogenpriorto storage.Immediatelybeforeuse,0.1 ml of this stannous solution was diluted with 10 ml ofnitrogen flushed saline resulting in a final concentration of100 pg stannous ion per ml at pH 4.3. The freshly preparedstannousion solutionwas then addedto the [@Tc]HSAsucralfate mixture at the time of mixing. A series of thesemixtures with varying pHs were prepared and analyzed forthe efficiency of[@mTc]HSAbinding to the sucralfate.

Effect ofspec@/Icactivity on f@mTc]HSA@sucralfatecomplexstability. Two preparations of stannous human serum albumm were prepared, the first as outlined in section la. Thesecond was preparedin an identical manner except that the99m1@f@@was replaced with saline. Varying proportions of each

ofthese solutions, such that their sum was always 1.4 ml, werethenincubatedwith38.5mgofsucralfate.Analysiswascarriedout after 1-hrrotationand after24-br storageat ambienttemperature.

Evaluation ofthe sucralfate capacityfor binding albumin.Technetium-99m-labeledHSA prepared as described in lawasmixedwithvaryingquantitiesof unlabeledHSAso thatthe total albumin content varied.This solution was then usedto form the rmTc]HSAsu@fate complex. The pH of the[@Tc]HSAandHSAsolutionswaskeptat4.3. Followingthe1-hr incubation the suspension was removed from the rotatorand an aliquot analyzed for the efficiency of complexation.

Optimizationof the (‘@“TclSucraIfateSynthesisEffectof stannousion concentration.Theamountof stan

nous ion generatedis directlyproportionalto the total electrical charge transmitted (7). In this seriesof experimentsthecurrent used to generate the stannous ion in the sucralfatesuspensionwasreducedto 1mA and the time variedfrom 15secto 2 mm. Upon completionofelectrolysis,the samplewasrotatedfor 1hrandthensampledforqualitycontrolanalysis.A secondqualitycontrolanalysiswas done 24 hr aftertheinitial preparation.

Effect ofspecj/ic activity on complex stability. A series of

The Journal of NuciearMedicine524 Billinghurst,Abrams,andLawson

ROCH2 ROCH2&—.o\@ I/°\@

@OR HA0@H R02@ @..II....@YCH2OR

H OR OR H

R= S03[A12(OH)5]FIGURE 1Structure of sucralfate.

MATERIALS AND METhODS

Preparationof LabeledSucralfateTechnetium-99m-labeled sucralfate was prepared both by

chemical binding of[@―Tc]HSAto sucralfate and by the directreaction of pertechnetate with sucralfate in the presence ofstannous ion. These investigational studies used only 38.5 mgofsucralfate as opposed to clinical levels of2SO to 1,000 mg.

Technetium-99m HSA-sucralfate(a) Technetium-99mHSAThisproductwaspreparedin a similarmannerto thatused

routinely in our nuclear medicine department. However, thefinal pH adjustmentand the addition ofdextrose wereomittedsince the binding ofalbumin to sucralfate occurs preferentiallyatacidicpH. Theprocedureusedwasas follows.

Humanserumalbumin(12.5 mg) was addedto 4 ml of@“TcO4(3 GBq, 8 mCi) in saline and 2 ml of iN HG in a

lO-mlsterile multidose vial into which two tin wire electrodeshadbeeninserted(electrolyticvial).Thesetwoelectrodeswereconnected to a constant current power supply and the vialplacedin an ultrasonicbathto providecontinuousmixing.Acurrent of 2 mA was then applied for 10 mm. The vial wasdisconnectedfromthepowersupply,removedfromtheultrasonic bath and allowedto stand for 5 mm. The resultant[@Tc]HSA was dilutedwith 18 ml of saline and filteredthrougha 0.2-micronsterilizingfilterunit (Nylon66 membrane;Micron SeparationsInc.).

(b) Linkageof[@mTcJHSAwithsucralfateThe [@mTcJHSA@sucralfatecomplexwaspreparedusinga

modified version of Vasquez et al. (1). Sucralfate (38.5 mg)was suspendedin 1.4ml of [@‘Tc]HSAand the suspensiondiluted to 10ml with sterilewater.The suspensionwas rotatedfor 30 mm to allow complexation of [@“Tc]HSAwith thesucralfate.

Direct labeling of sucralfate with /@mTcJpertechnetate(f99mTc]sucra@f@@te)

Sucralfate (38.5 mg) was suspended in 6 ml of salinecontaining 0.2 GBq (5.5 mCi) of @TcO4in a 10-mi sterileelectrolytic vial. A currentof4 mA was applied for 0.5 mm.

Analysisof the LabelingEfficiencyof theSucralfate Complexes

The sucralfatesuspension was rotated to ensure thoroughmixing, then 0.2 ml was withdrawn and applied to a 0.2-

TABLEI[@Tc]SucraIfateLabeling Efficiency as a Function of

IncubationTime of [@‘TcJHSAandSucralfate99mTcboundIncubation

timeSto(mm)sucralfate(%)t

. 0.73 mg I@Fc]HSA and 38.5 mg sucralfate were rotated at

ambienttemperatureforthe appropriatetime.t % Binding efficiency was calculated as the % of the total

activityboundto the fifterafterpassinganaliquotof the suspensionthrougha0.2-smembranefilter(MSI).

experiments were conducted to determine at what specificactivitythe24-hrstabilityof[@―Tc]sucmifatewouldbe compromised. Technetium-sucralfate preparations using 0.01 @igof stannousion (1 mA, 15 see) werepreparedwith varyingamounts of @Tc.Analysiswas carried out after 1 hr and24 hrincubationat ambienttemperatures.

Comparison of @TcJHSASucralfateand @“TclSucraIfateStability

Stabilityat variouspHs.Thestabilityofeach ofthe @“Tclabeled sucralfate complexes at various pH values was cornpared. Both products were prepared under optimum conditions,centrifuged,andthe supernatantin whichthe labelinghad been conducted was removed by aspiration. The labeledsucralfatewas then resuspendedin 10 ml of aqueous salinesolutionat the appropriatepH. The pH of the salinesolutionhad been previously adjusted with either HC1 or NaOH. Theresultingsuspensionsweremtatedfor20 hrandsampleswereremoved for quality control analysis at 1 and 20 hr. Theanalysis consisted of the evaluation of the @“Tcbindingefficiencyto the sucralfateand the determination of the pHof thesuspension.

Stability with respect to the exchange with albumin. The@Tc-labeledsucralfatecomplexeswerecentrifuged,the su

pernatant removed and resuspended in saline solution contaming various amounts of HSA. These suspensions wererotated for 20 hr and analyzedat 1hr and 20 hr.

RESULTS

Optimr'ation of the Conditionsfor Preparationof@Tc1HSASucralfate

Effect ofincubation time. Quality control data takenat various times after the initial mixing of [@Tc]HSAto sucralfateare shown in Table 1. These clearly mdicate that the binding of [@“Tc]HSAto sucralfate is arapidprocess. In furtherstudies, a 30-mm rotation timewas adopted as a matter of convenience.

Effect ofpH. The results shown in Figure 2 indicatethat quantitative binding of [@“Tc]HSAto sucralfaterequired a pH of 95%). Limited dissociation of the radioactive labeloccurred between pH 9 and 10. In contrast, [@“Tc]HSA sucralfate showed significant loss of the radioac

5101530

97.198.398.798.8

525VoIume3O•Number4 •April1989

99mTcboundRadiOaCtIVitytosucralfatet

%MBqMBqjmg (mCi mCi/mg) 1 hr 24 hr

>-

C.)zwC)LI.LL@w

zz

. Concentration of HSA in each preparation was kept constant

(0.5mg)wh@etheamountof @‘1@cwasvaried.38.5mgsucralfateusedineachexperiment.

t % Binding efficiency was calculated as the % of the total

actMtyboundto the filterafterpassinganahquotof the suspensionthrougha0.2-gimembranefifter(MSI).

100

FIGURE 2Effectof pH on the bindingefficiencyof [@“‘Tc]HSAto sucralfate. (Y) I 01L9 Stannous ion added to the suspension;(U)withoutaddedstannousion. Sucraitate (38.5 mg) was addedto [@Tc]HSA [200 MBq (5.5 mCI),0.5 mg] pH adjustedand incubatedat ambienttemperaturefor 1 hr tothe appropriate pH. The % bindingefficiencywascalculatedasthe% ofthe total activity bound to the filterafter passing an aliquot of the suspensionthrougha 0.2-i membranefilter (MSI).

75

50

25

4.4 5.0 6.0 7.0 8.0

pH

tive label when the pH of the suspending solution wasabove six.

Stability against exchange with HSA. The stability ofthe radiolabelon 99mTclabeledsucralfatewas evaluatedby competition with HSA. The results shown in Table4 indicate that for [@mTc]HSA@sucmifatethere was nosignificant loss of the label. In contrast, the fraction of99mTc bound to sucralfate decreased nominally from98% to 83% within 1 hr and to 72% after 24 hrincubation. These suspensions were then centrifugedand the supernatant analyzed by instant thin layerchromatography (ITLC) using methyl ethyl ketone(MEK) and saline as independent solvents. The radioactivity which dissociated from the sucralfate was @@.‘30%pertechnetate and 70% [@mTc]HSA.

DISCUSSION

Sucralfate may be labeled using the original approachof Vasquez et al. (1) involving the binding of labeledprotein to sucralfate or by the direct labeling of @“Tcto sucralfatein the presence of stannous ion. It was thepurpose ofthis study to evaluate each production technique and to characterizethe two @Tc-labeledpreparations. Neither method requiredsignificant incubationtime to achieve maximum binding efficiency. However,in terms oftechnologist time, it must be recognizedthatthe preparationof[@―Tc]HSAis an additional step andcomplicates the overall labeling procedure.In addition,it is important to note that the binding of labeledprotein to sucralfate requires that the protein solutionhave a pH

. 38.5 mg Sucralfate m normal saline at pH 4.3 and 300 MBq

(8mCi) @tCO4.t Stannous Ion (SnQ@)was prepared by dissolution of 0.5 g tin

metalin4 mlconcentratedH@anddilutedto 50 mlwithnitrogenflushedsaline.

* % @Jog efficiency was calculated as the % of the totalactivityboundto the filterafterpassingan aliquotof the suspensionthrougha0.2-smembranefilter(MSI).

100

0z

U)I

FIGURE3HSAbindingefficiencyof sucralfate.[@9―1cJHSAwasdilutedwith increasingconcentrationsof unlabeledHSAand Incubated with a constant concentration.ofsucralfate(38.5mg)atpH4.3forl hr. The% binding efficiencywas calculatedas the % ofthe total activity bound to the filter

1000 1200 1400 1600 1800 after@*$S$ng@flalk@UOtOftt*S*Js

pensionthrougha 0.2-,@membraneMOLAR RATIO (SUC/HSA) filter (MSI).

80

60

40

20

00 100 200 400 600

The original publications on labeled sucralfateas anulcer imaging agent based the formation of the labeledspecies on the affinity of sucralfate for HSA. Thisaffinity for protein is also the basis for the use ofsucralfate in ulcer therapy. Therefore, the same featureis used for both the labelingand the in vivo localization.Thus, it is possible that if the molecular ratio of theHSA to sucralfate used for labeling was too high thenthe in vivo binding to the ulcer site would be compromised. The study of the binding efficiency of [@Tc]HSA to sucralfateas a function of HSA content showsthat quantitative binding occurs up to a molar ratio of1:400 HSA to sucralfate (i.e., sucralfate will bind up to-..-7%ofits own weight ofalbumin). It must be remembered however, that sucralfate is an insoluble powder.This means that the affinity of sucralfate both for HSAand the protein ofthe denuded mucosa is not a function

of the total sucralfate mass but of the surface area.In vitro, at pHs above 3, this surface area is a factor ofthe powder size (i.e., the finer the powder, the greaterthe surfaceareaand henóethe largerthe HSA capacity).Thus, the molar ratio reportedhere of 1:400 representsonly a rough guide and it would be wise to keep theHSA content in clinical preparations well below thisvalue. It should also be rememberedthat upon exposureto the acidity of the stomach, the sucralfate powderforms a sticky amorphous substance which will havesubstantially less surface area than the relatively finelydivided powder. Although some of the HSA moleculesattached to the sucralfate in the powder form willcertainly be contained within the matrix ofthis glutenous mass it is also realistic to expect that the sucralfatemolecules which make up the surface of the mass willlargely be molecules which were on the surface of thepowder particles. Therefore it is unlikely that the ratioof the sucralfatemolecules to which an HSA moleculeis bound to those which are not associated with an HSAmolecule will change favorably. Since the binding limitin the powder form is -‘-7%on a weight basis, it wouldbe prudent to keep the mass of HSA to

V

.

V00

C.)I—

E0)0)

z:@0 V

75

5

FIGURE 4Effect of @Tcconcentration on[@“Tc]sucralfatestability. (•)1 hr incubation; (Y) 24 hr incubation. Sucralfate (38.5 mg) was labeled withincreasing concentrations of @“Tcinthe presence of 0.01 @igstannousion. The % binding efficiencywascalculated as the % of the total activity bound to the filter after passinganaliquotof the suspensionthrougha 0.2-ti membranefilter(MSI).Thearrow indicates the @“‘Tcconcentratin at which [@“Tc]sucraIfatedemonstrated24 hr instability.

V

VV

V

It

1 2 3

99m Tc (GBq)

saturation (Fig. 3), yet, loss of @“Tcfrom [@“Tc]sucralfate was observed (Table 4). Analysis of the unbound 99mTcrevealed that this radioactivity was predominantly [99mTc]HSAsuggesting that transchelationhad taken place. However, the lowest level ofHSA usedwas four times the HSA saturation level for sucralfate.It would seem that this is unlikely to be a problemwhen the radiopharmaceutical is given to fastingpatients. However, this should be considered inunexpected findings and does represent a significantdifference with respect to the properties of the twoformulations.

Since there is interest in imaging sites of ulcerationin not only the stomach but also the duodenum andileum, it must be recognized that not only must theradioactive label on the sucralfatebe stable at the lowpH of the stomach but it must also be stable at thesignificantly higher pH encountered in the duodenumand ileum. In his report on the characteristics of sucralfate, Nagashima (6) noted that the binding of sucrose octasulfate to HSA dropped rapidly at a pH over4. We have demonstrated that for satisfactory labeling,a pH below 5 was required.That it was possible to havea pH as high as 5 and still have satisfactory labeling wasalmost certainly a result of the excess sucralfate overHSA in these preparations. In addition, it would beanticipated that the [@“Tc]HSA-sucmifateformed atlower pH may well dissociate if the pH of the environment is raised. Indeed, the data in Figure 5 indicatesthat above pH 6 significant decomposition occurs de

pendent on the pH. Thin layer chromatographicanalysis of the radioactivity released from sucralfateat thesehigher pHs indicated that it was [99mTc]HSA. Thisconfirmed that the loss of radioactivity from sucralfatewas due to rupture of the HSA-sucralfate bond. Thesefactswould suggestthat if[@―Tc]HSA-sucralfateis usedto image the duodenum and ileum we should expect tosee a small percentage of activity due to [@TcJHSAbesides that associated with sucralfate. No release of

@Tcfrom [@TcJsucraffateat a pH below 9 was notedin a similar study. Therefore, if the diagnostic testincludes imaging of the duodenum or ileum there maybe less chance of artifacts due to radioactivity notassociated with sucralfate if the directly labeled [@mTc]sucralfate is employed.

Pera et al. (4) first reported the direct labeling ofsucralfate with @Tcin the presence of stannous ion.They showed that it worked as an in vivo labelingprocess. In this approach, the sucralfate, mixed withstannous ion was administered to the patient, then 2 hrlater, @TcO4was administered. In the empty stomachat low pH, the stannous ion will likely remain asstannous ion and therefore successfully bind the @“Tcwhen administered orally. However this technique maynot be useful for evaluation of inflammatory boweldisease since the pH rises in the bowel and as a resultthe stannous ion will be increasingly subject to hydrolysis. This will result in the lack of binding of @“Tctothe sucralfatethat has left the stomach priorto exposureto pertechnetate. In vivo animal studies are necessary

528 Billinghurst,Abrams,andLawson The Journal of Nuclear Medicine

CompetitionofTABLE4

HSAwith [@Tc]HSA[@“Tc]SucraIfate

[99mTcJHSAsucralfat&-Sucralfate

and

[@9―1@c]sucralfatetHSA%

Bound%Boundconcentration9amTc$9@@Tc4(@imol)1

Hr 24 Hr1 Hr 24 Hr

. 1 6 @mo1 Sucralfate labeled with 0.01 1 @mol [@Tc]HSA.

t 16 @molSucralfate labeled directly with@

* % Binding efficiency was calculated as the % of the totalactivityboundto thefiRerafterpassinganaliquotof thesuspensionthrougha 0.2-,@membranefilter(MSI).

100

EC)C)0z

a

75

50

I 0.0

pH

FIGURE 5Effectof pHon the stabilityof [@“‘TcJHSA-sucralfate (•)and [@“TcJsucralfate (V) 1 hr(A) and 24 hr (B)afterpreparation. Both [@rc]HSA-sucralfate and [@“Tc]sucralfatecornplexes were prepared under optimum conditions.The preparationswere centrifuged,the supernatantwas removed and the product wasresuspendedin 10 ml normalsalineat theappropriatepH.The% bindingefficiencywascalculatedasthe % ofthe total actMty bound to the filterafterpassingan aliquotof the suspension through a 0.2-s membranefilter (MSI).

C)

C)0z:@0

to confirm these suggestions. However, until such resuits are available it would be wise to avoid the use ofthe in vivo labeling approach when the purpose of thestudy is other than the detection ofgastric ulceration.

2.0 4.0 6.0 8.0 10.0

pHb

CONCLUSION

Both formulations of @Tc-iabeled sucralfate provided a readilypreparedproductwhich was stableunderacidic conditions such as encountered in the stomach.It is worth noting that some caution should be exercisedwith [@Tc]HSA sucralfate. It is recommended that theratio of sucralfate to HSA be kept above 100 to 1 anda fine sucralfate powder be employed. Clinically, it islikely that the distinction with respect to the utility ofthese agents will be observed in the imaging of thebowel where the pH rises. Once the pH exceeds 6 thereis a tendency for the HSA to dissociate from the sucralfate.This would be expected to give rise to artifactsand/or undesired background radioactivity in the imaging of the bowel, especially the lower bowel. On theother hand, [@TcJsucra1fate shows good stability ashigh as pH 9 and is therefore unlikely to experiencedissociation in the bowel. Although under normal circumstances, transchelation is not likely to be a majorconcern, it should be remembered that [@Tc]HSAsucralfatedoes show greaterresistanceto transchelationthan does [@Tc]sucmifate (Table 5).

0.0098.699.398.097.20.2197.599.283.373.80.4296.698.782.471.30.6396.196.686.973.50.8499.294.483.471.41

.0499.092.682.172.3

529Volume 30 •Number 4 •April1989

[@“Tc]HSA[99mTc]Factorsucralfatesucralfate

TABLE5Comparisonof [@‘Tc]HSA-Sucraltate

and[@‘Tc]Sucrallate

ACKNOWLEDGMENTSThis workwas supportedin partby the HealthSciences

Centre ResearchFoundation. The authors thank Ms. SusanD. Joy for her patiencein typingthis manuscript.

REFERENCES1. Vasquez TE, Beidges RI, Braunstein P, et al. Gas

trointestinalulcerations:detectionusinga technetium99m labeled ulcer avid agent. Radiology 1983;148:227—231.

2. Puttemans N, Lambert M, Andre PP, et al. Detectionof gastroduodenalulcers using technetium-99m labeied sucralfate. JNuclMed 1987; 28:52 1—523.

3. Dawson DJ, Khan AN, MillerV, et al. Detection ofinflammatory bowel disease in adults and children:evaluation of a new isotopic technique. Br Med J1985;291:1227—1230.

4. Pera A, Seevers RH, Mayer K, et al. Gastric ulcerlocalization by direct in vivo labeling of sucralfate.Radiology 1985; 156:783—786.

5. Vasquez TE, Pretorius HT, Greenspan G. Radiolabeled sucralfate: a review of clinical efficiency. NuciMed Commun 1987; 8:327—334.

6. Nagashima R. Development and characteristicsofsucralfate.J Cliii Gastroenterol1981;3:103—110.

7. Vogel Al. A textbook ofquantitative inorganic analysis. 3rdEdition.London:Longmans,1961:589.

8. Billinghurst MW, Rempel S, Westendorf BA. Radiation decomposition of technetium-99m radiopharmaceuticals.JNuclMed 1979;20:138—143.

Com@@exityTimeStannousion

Labeling protocol

— +

— +

+ +

Preparationstability+

+ ++

pHSpecific.activityLabelexchange

Summary1. [@“Tc1Sucralfaterequiredlesstimeandhandlingto prepare

than [@‘Tc]HSA-sucraUate.2. [“@‘Tc)Sucralfatewasmorestableat thehighpHthatwould

be encounteredinimagingofthe bowel.3. [@‘Tc]HSA-sucraltatewasmoreresistantto lossof labelto

exogenousprotein.

. No breakdown of the [@TcJHSA-sucr&fate complex was

observedat the highest @Tcconcentrationachievableunderstandardconditions.

530 Billinghurst,Abrams,andLawson The Journal of Nuclear Medicine