Splenic scintigraphy using Tc-99m-labeled heat-denatured red blood cells in pediatric patients: concise communication.

Abstract

Ten children underwent splenic imaging with heat-denatured red blood cells labeled with technetium-99m (Tc-99m DRBC). The presenting problems included the heterotaxia syndrome, recurrent idiopathic thrombocytopenic purpura following splenectomy, mass in the left posterior hemithorax, and blunt abdominal trauma. In nine patients, the presence or absence of splenic tissue was established. A splenic hematoma was identified in the tenth patient. All patients were initially scanned with Tc-99m sulfur colloid (Tc-99m SC), and were selected for Tc-99m DRBC scintigraphy only after the results of the SC scans failed to establish the clinical problem beyond doubt. The availability of kits containing stannous ions, essential for efficient and stable labeling of red blood cells with Tc-99m and requiring only a small volume of blood, make splenic scintigraphy in children a relatively simple and definitive diagnostic procedure, when identification of splenic tissue is of clinical importance.

Full text

Page 1

Technetium-99m sulfur colloid (Tc-99m SC) is the
most commonly used radiopharmaceutical
of the spleen. Following intravenous administration, it
is rapidly removedfrom the blood by the reticuloendo
thelial system of the liver, spleen, and (to a much lesser
extent) bone marrow. Thus, the spleen is adequately
visualized and its image can usually be separated from
that of the adjacent liver in patients with normal upper
abdominal anatomy. In certain disease entities, however,
this is not the case and selective imaging is desirable.
Although splenic imaging with radiolabeled
cells (RBCs) has been available for over 20 yr (1—6), it
is only recently that advances in radiochemical tech
niques have made it a practical examination.
Chromium-5 1 was the first radionuclide
successfully for the labeling of intact and heat-denatured
RBCs for both in vitro and in vivo studies (2, 7—9).
Chromium-5 I, however, is an unsatisfactory imaging
for imaging
red blood
to be used
Received Aug. 14, 1981; revision accepted Oct. 23, 1981.
Forreprintscontact:NicholasPapanicolaou, MD, Div.of Nuclear
Medicine, Children's Hospital Medical Center, 300 Longwood Ave.,
Boston,MA 02115.
agent because of its low photon flux, energetic gamma
rays (320 keV), and long half-life (Tip
Later, technetium-99m was used for the same purpose
(5, 6). Unfortunately,the binding efficiency
to the RBCs turned out to be less than 25%. The intro
duction of reductive methods using stannous ions (10)
led to the development of improved methods for binding
Tc-99m to red cells. This technique has been used suc
cessfully in several institutions for gated cardiac and
gastrointestinal bleeding studies as wellas measurements
of RBC mass. Heat-denatured red blood cells prepared
after labeling with Tc-99m with the same kit have been
used for splenic imaging in adults (11—13). A problem
with that method, as applied to infants, is that it needs
6—8 ml of whole blood. We present our early clinical
experiencewith a modification
tional Laboratory (BNL) method more appropriate for
the small blood volumes of neonates and infants.
27.8 days).
of Tc-99m
of the BrookhavenNa
MATERIALSANDMETHODS
Ten patients were studied. Relevant clinical data are
shown on Table 1. All patients were initially imaged
Volume23, Number 3
209
Splenic ScintigraphyUsingTc-99m-Labeled Heat-DenaturedRedBloodCells in
PediatricPatients:Concise Communication
ConradP.Ehrlich,NicholasPapanicolaou, S.Treves,RogerA.Hurwitz,andPowellRichards
TheChildren'sHospitalMedicalCenterandHarvard MedicalSchool,Boston,Massachusetts andBrookhaven National
Laboratory, Upton, New York
TenchildrenunderwentspienicImagIngwithheat-denaturedredbloodcellsIa
beledwithtechnetium-99m (Tc-99mDRBC).Thepresenting problems included
the heterotaxia syndrome,recurrent idiopathicthrombocytopenicpurpurafol
lowing splenectomy, mass in the left posterior hemithorax, and blunt abdominal
trauma. In nine patients,the presenceor absence of splenictissuewas estab
lished A splenic hematoma was identified In the tenth patient. All patients were
initiallyscannedwith Tc-99m sulfurcolloid(Tc-99m SC), and were selectedfor
Tc-99m DRBCscintigraphy onlyaftertheresultsoftheSCscansfailedtoestablish
theclinical problem beyond doubt. Theavailability ofkitscontaining stannous Ions,
essential for efficient andstable labeling of red blood cells with Tc-99m andrequir
logonlyasmallvolume ofblood, makespienic scintigraphy Inchildren arelatively
simpleanddefinitivediagnosticprocedure,whenIdentificationofsplenictissueis
ofclinicalImportance.
J Nucl Med 23: 209—213,1982

Page 2

Case Age SexClinical DiagnosisH-JBodiesSCScanDRBCScan
New
151015born
Adyr ministyr ereddyr ose (mCi)yr
EHRLICH, PAPANICOLAOU, TREVES, HURWITZ,AND RICHARDS
111 dMheterotaxia, r/o asplenia
+asplenla
polysplenia,RUQ
premature
5mo
9d
premature
Smo
41/4 mo
21/2 yr
2yr
2
3
M
M
heterotaxia, r/o asplenla
heterotaxia, r/o asplenia
—
+
asplenia
asplenla
polysplenia, RUQ
asplenia
+
notdone
+
+
4
5
6
7
F
F
M
F
heterotaxia, r/oasplenia
heterotaxia, r/oasplenia
heterotaxia, r/o asplenla
recurrent1W,
postsplenectomy
recurrentlW,
p0@@
r/osplenichematoma
Ieftthoracicmass,r/o
hepaticorsplenlc
herniatlon
8l3yrF
9 l6yr
21d
F
M10
asplenia
asplenla
asplenia
asplenia
asplenia
asplenia
asplenia
asplenia
+smallsplenule
smallsplenule
notapplicable
notapplicable
equivocal splenic defect
massiseitherliveror
spleen
positive splenic defect
massidentifiedas
spleen
Notes:DRBC= heat-denatured redbloodcells;H-J
upper qua&ant; SC sulfur colloid; r/o
Howell-Jolly; 1Widiopathic thrombocytopenic purpura; RUQ right
rule out.
previously reported
denaturation, the efficiency drops slightly to 90% (per
sonal communication, P. Richards). Administered dose
and absorbedradiationdoses to the spleen and whole
body are given in Table 3.
Imagingbegan 30 mm after the injection
to be at least 95% (1 1). After heat
and was
using Tc-99m
imaging was then performed because the SC scan was
inconclusive. Parents or guardians of each patient were
informed of the potential risks and benefits of the
study.
The method of preparation isoutlined in Table 2.The
main difference between the adult method and the pe
diatric version presented here is that only 1ml of blood
is sufficient for the latter. The labeling efficiency with
the BNL kit before heat-damaging ofthe RBCs has been
sulfurcolloid(SC).Selective splenic
TABLE2.
Preparation ofTc-99mDRBC forPediatric Usewiththe
BNLKit
1. Add 8 ml of normal saline to a BNL kit.
2. Withdraw 2mlofthissolutIon andInjectit intoa3-mi
sterile glasstube.
3. Add1 ml of heparinized wholebloodintothe3-mI
tube.
4. Gentlyrotatethetubefor 10mm.
5.CentrIfugethetube for 5 mm (1200—1500
6. UsIng along needle, &awthepacked RBC Into asyringe
(donotremoveplasma).
7. Add thepacked RBC intoanother tube containing 1mlof
Tc-99m as NaTcO4(seeTable3 for mCI).
8. Gently agitate thetubefor5mm.
9. Incubatethetubefor 12—15 mmInconstant-temperature
bathat49.5° C.
g).
BNL
DRBC= heat-denatured redbloodcells.
Brookhaven NationalLaboratory;
Tc-99m SC
Tc-99mDRBC
Critical-organ
dose(red)
Tc-99m SC(liver)
Tc-99mDRBC(spleen) 4.0
Whole-body
dose(rad)
Tc-99mSC
Tc-99mDRBC
1.8
0.4
0.1
0.9
0.2
1.3
0.3
1.8
0.4
2.5
0.5
1.2
3.0
1.2
2.6
1.0
2.4
1.0
2.0
0.059 0.05
0.036 0.025 0.019
0.05 0.049 0.05
0.017 0.012
. FromWebsterEW,AlpertNM,BrownellGL: Radiation
dosesinpediatric nuclear medicine anddiagnostic x-ray
procedures. InJamesAE,WagnerHNJr.,CookeRE,Eds:
Pediatric Nuclear Medicine.Philadelphia,W. B. Saunders,
1974, pp34—58.
t FromtheRadiopharmaceutical
formation Center, OakRidge, TN.Assumption: splenic uptake
of Tc-99m DRBCIs90% of the injecteddose.
Internal DosimetryIn
210
THEJOURNALOF NUCLEARMEDICINE
TABLE1.
TABLE3. RADIATION ABSORBED DOSEFOR
Tc-99mSULFUR COLLOIDHEAT-DENATURED
REDBLOODCELLSt

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ClINICAL
NUCLEAR
SCWNCFS
MEDICINE DIAGNOSTIC
when thrombocytopenia
raised the question of a splenule in the left upper quad
rant. The DRBC study was then performed in an effort
to locate any splenic tissue before a second laparotomy.
It clearly demonstrated the presence of one discrete,
small spleen (Fig. 3B). At surgery, a splenule I cm in
diameterwas found and removed.
The infant with the left inferoposterior
mass—discovered on a chest radiograph obtained for
evaluation of mild respiratory distress—underwenta SC
scan. The radiographic abnormality was shown to con
tam reticuloendothelialsystem cells, indicating the
presence of either hepatic or splenic parenchyma. It was
positively identified as the spleen only by the DRBC
study (Fig. 4). In the patient sustaining blunt abdominal
trauma who had a questionable splenic defect suggesting
a hematoma by the SC scan, the DRBC study clearly
demonstrated the abnormality.
recurred, a repeat SC scan
thoracic
DISCUSSION
Congenital asplenia and polysplenia are most fre
quently associated with the heterotaxia syndrome (14).
In a pathologic study of 51 patients with heterotaxia
(15), Freedom found asplenia in 32 (63%), polysplenia
in 9 (17%), rudimentary spleens in 7 (14%), and normal
spleens in 3 (6%). As an autopsy series, the group has
more complex lesions with asplenia.
Asplenia, congenital or acquired, is associated with
an increased risk of sepsis (16), whose incidence in
creases with the severity of the underlying condition and
decreases with age (17, 18). In children splenectomized
for trauma, 1—2% develop sepsis (19). Of 52 patients
with asplenia syndrome seen at the Boston Children's
Hospital Medical Center (CHMC) between 1950 and
1975, 12 (23%) died ofsepsis (20).
Tc -99mSulfur CoIIo@d
Tc - 99mheatedt)Icodccl I@
Ap
Asplenia
FIG. 1. Heterotaxiawith asplenla.Five-month-old female with
complexcongenital heartdiseaseandmidlineliver.Sulfurcollold
scan(toprow)showsnodiscerniblesplenictissue.Heat-treated
ABCs(bottomrow) confirm absenceof selective splenic uptake.
performed with a gamma camera equipped with a
high-resolution collimator. Multiple views were always
obtained to provide optimal delineation of the anatomy
in the upper abdomen. In patients with splenic tissue, its
radionuclide uptake was intense and increased with time
over a period of 90— 120 mm. In asplenic patients there
was prolonged visualization of the blood pool and
liver.
RESULTS
Six patients with the heterotaxia syndrome had no
demonstrable splenic tissue on SC scan; two were found
to have spleen(s) with the DRBC study (Figs. 1and 2).
Two patients with recurrent idiopathic thrombocyto
penic purpura (lIP) were imaged following splenecto
my. One of them was asplenic by both methods. The
other patient appeared to be asplenic by SC scan im
mediately followingsplenectomy, but sevenmonths later,
FIG. 2. Heterotaxia with spleen. Eleven-day-old male with dextrocardia and midline liver. Sulfur colloid scan (top rowj shows distinct
splenic visualization. Heat-treatedRBCs(bottom row) demonstrate Intenseradlonuclide uptake by splenic tissue In the right upper
quadrant.
Volume23, Number 3
211
Ic-SC
AP RLat.
Tc-heatedred blood cells

Page 4

Tc-99m
Swl@,
Collold
.@.
-@
@A@,.
...H.r.Iotl...1
EHRLICH, PAPANICOLAOU, TREVES, HURWITZ,AND RICHARDS
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splen.ct.my Ta-SCI
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9—Is—so @;@h.1•;.
— ...@,.r?@
A
LAO
L LAT
Pa
FIG.3. Recurrent idiopathic thrombocytopenic purpura (ITP)following splenectomy In13-yr-old female.A:sulfur colloid scanimmediately
aftersplenectomy (toprow)showsaspleniaRepeat scanning 71/2 melater,afterrecurrence ofsymptoms, shows faintlyfocalaccumulation
ofradionuclide Inleftupperquaci@ant,bestseeninleftlateral andposterior oblique projections. Itwassuggestive ofasplenule. B:heat-treated
ABCsclearly show Intensefocal uptakeby splenule,confirmed bya secondIaparotomy.
Advances in cardiac surgery are increasing not only
the survivalofchildren, but also the years at risk forthem
to develop serious infections. The diagnosis of asplenia
is therefore no longer of purely academic interest. Cur
rent recommendations for the management of such
children include prophylactic antibiotics and pneumo
coccal vaccination(16, 20).
The diagnosis of asplenia may be strongly suggested
by a peripheral-bloodsmear showing Howell-Jolly
bodies. However, these infrequent, intra-erythrocytic
nuclear remnants may also be found in peripheral-blood
smears of premature, and even full-term, babies with
intact spleens (21). A more direct approach to comple
ment the clinical and laboratory impression is splenic
scintigraphy (22). During the past 5 yr. 33 patients with
complex congenital heart disease at the CHMC under
went SC scans to rule out asplenia. The spleen was
identified in 27of them (82%) (unpublished data). In the
FIG 4. Leftintrathoracic massin3-wk-old
Infant. Sulfur colloid scan shows massto
containreticuloendothellal systemcells.
Distinctionbetweenliverandspleenisnot
possible(toprow, bestseenon left lateral
view). Heat-treatedRBCsdemonstratein
tenseradionuclide uptake bya partially
Intrathoracic spleen.
212
THE JOURNAL OF NUCLEARMEDICINE

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CLINICAL
NUCLEAR
SCIENCES
MEDICINEDIAGNOSTIC
remaining patients some doubt existed evenwhen the SC
scan was supplemented with agents selectively imaging
the liver,such as 1-131rose bengal. It is in these children
that selective scanning of the spleen is advantageous.
The utility of splenic imaging is not limited to the
heterotaxia syndrome. The Tc-99m DRBC study may
be useful to assist a search for accessory spleens or
splenosis in hematologic diseases that require splenec
tomy (23). For instance, nearly 70%of the patients with
ITP may benefit from total splenectomy (24). Therefore,
a DRBC scan may be indicated to facilitate complete
removal of splenic tissue. We also anticipate that by the
same technique one could locate any splenic tissue left
behind or regeneratedafter an earlier splenectomy.
Furthermore, selective imaging of the spleen is defi
nitely superior to the SC scan when the latter isdifficult
to interpret owing to masking of the spleen by an over
lyingleft hepatic lobe.This was shownboth inthe patient
with the splenic hematoma and in the infant with the
intrathoracic mass.
The requirement of only small amounts of blood for
the BNL kit is clearly an advantage with neonates and
infants.We recommend this procedure
method complementary to the SC scan whenever there
is reasonable doubt about the latter's ability to establish
the presence or absence of splenic tissue.
as an imaging
ACKNOWLEDGMENTS
TheauthorsthankMr. RoyalDavisfor histechnicalassistance and
Mrs. Laurie Pugsleyfor preparationof themanuscript.
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