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Simplified Technetium-99m-EC Clearance in Adults from a Single Plasma Sample
Levent Kabasakal, A. Fuat Yapar, Kutlan Özker, Ebru Alkan, Saadet Atay, Nihat Özçelik and çetin Önsel
J Nucl Med. 1997;38:1784-1786.
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Simplified Technetium-99m-EC Clearance in Adults
from a Single Plasma Sample
Levent Kabasakal, A. Fuat Yapar, Kutlan Ozker, Ebru Alkan, Saadet Atay, Nihat Ozcelik and cetin Onsel
Department ofNuclear Medicine, Cerrahpa@,caMedical Faculty, Istanbul, Turkey
Technetium-99m-EC has recenfly been introduced as an alternative
renal tubular agent to 131l@.@ iodohippurate (OlH). It has been
shown that
@Tc-EC
clearanceshows strong correlation with OIH
clearance and it is possible to estimate effective renal plasma flow.
In routine clinical studies, it is practical to use one or two plasma
sample methods instead of multiple plasma samples for clearance
determination. An attempt was made to determine °@‘Tc-EC
clear
ance with one sample method. Methods Data from 72 subjects
were collected. To increase the range of renal function, two anuric
hemodialysis patients were also included. Clearanceswere deter
mined by the open two-compartment model. Results The clear
ance rangewas 12 mVminto660 mVminwith amean of275 ±117
mVmin. Analysis of correlation was made by Tauxe's method. The
least standard error of estimation (s.e.e. = 32.71 mVmin) and the
best correlation (r = 0.97) between the theoretical volume distribu
tion and the clearance estimations were obtained from the 54-mm
plasma sample. Conclusion: This study suggests that EC clearance
couki be determined by a simplified single-sample method with an
acceptable s.e.e.
Key Words technetium-99m-ethylenedicisteine; clearance deter
mination; radionuclide renography; effective renal plasma flow; renal
function
J NucI Med 1997;3&1784'-1786
Subjects were injected with 200 MBq
@Tc-ECwhen scintig
raphy was performed and 5 MBq @mTc@EC
when scintigraphy was
not performed. Injection was through a three-way stopcock con
nected to an intravenous catheter and then flushed with saline.
Subsequently, 11 blood samples were obtained from 26 subjects,
and 7 blood samples were obtained from 44 subjects for a period of
60 mm. Anuric patients were studied for 180 mm, and 16 blood
samples were obtained from them. Blood samples were centri
fuged, 0.2-ml plasma samples were weighed and plasma radioac
tivity (C) was determined by counting the samples in a well
scintillation gamma counter. The injected dose (ID) was estimated
from the weight difference of syringes before and after the
injection and from a standard activity that was prepared at the time
of injection and diluted in 100 ml to 250 ml saline. The data were
plotted against time and rate constants (a and @3),
and the intercepts
(A andB) for slow andfast componentswere calculatedby using
the bi-exponential curve fit analysis. An open two-compartment
model suggested by Sapirstein et al. (10) was used for plasma
clearance determination. The theoretical volume distribution (ID/
Ce),for 1-mmintervalsup to 95 mm, was calculatedby using the
formula:
C@= A e@ + B
Eq. 1
An exponential fit, in the form of the formula suggested by
Technetium-99m-ethylenedicisteine
(@Tc-EC)
isanew
renalTauxe
et al. (8), was carried out for estimation of clearance from
tubular agent introduced as a substitute for ‘31I-orthoiodohip
purate (OIH) (1). Human studies of 9@Tc-EC showed consid
erable promise as a 99mTc replacement for ‘311-OIH
(2—5).It
has been demonstrated that the pharmacokinetics of 99mTc@EC
in determination of effective renal plasma flow is better than
those of 9@'Tc-mercaptoacetylthglicine (@Tc-MAG3),
and
renal extraction efficiency is higher, with a value of 70% (1—7).
High-quality images, low liver retention and ease of preparation
at room temperature with high labeling efficiency are the other
advantages of 9@Tc-EC over
@Tc-MAG3(2—7).
The quantitative renal function with renal radiolabeled agents
is widely used. However, the multiple-sample method is not
practical for quantitative routine renal function determination.
To overcome this limitation, one or two plasma sample methods
have been used as simple and accurate procedures for routine
clinical use (8,9). This study was performed to develop a
simplified single plasma sample method for estimation of
9@Tc-EC plasma clearance.
MATERIALS AND METhODS
Seventy-two subjects (41 men, 3 1 women; age range 17—59
yr)
participated in this study; 58 had various degrees of renal impair
ment, including 8 transplantpatients. All subjects had been referred
to our department for routine kidney function evaluation. To
increase the range of renal function, 2 anuric hemodialysis patients
and 14 normal subjects were also included in the study. The study
protocol was approved by the Medical Faculty Ethical Committee.
Received
Jul.12,1996;revisionacceptedFeb.24,1997.
For correspondence
or reprints contact: Levent Kabeaaka@ MD, Cerrahpa@a Tip
FakOlteSi, NUkIeer Tip Mabilim Dali Aksaray Istanbul, 34303 Turkey.
1784
calculated theoretical volume distributions as follows:
F = F@[l —exp( —a((ID/C@)
—V1@))],
Eq. 2
where F is the clearance, Fm,@is an asymptotic maximal value of
@‘Tc-EC
clearance, a is the rate constant slope and VIag @5
the
intercept of the fitted curve on the abscissa derived iteratively by
the Gauss-Newton method.
Statistical analysis was performed by conventional regression
analysis (p < 0.05, 95% confidence intervals).
RESULTS
Seven or more plasma samples of9@Tc-EC clearance ranged
from 12 ml/min to 660 ml/min with a mean value of 275.5 ±
1174 ml/min. The mean clearance range for the normals was
392.8 ± 118.3 ml/min. Figure 1 depicts the s.e.c. against
various sampling times). From these data it can be seen that the
nadir of the s.e.e. is between 50 and 60 mm. The least s.e.c. of
@‘Tc-EC
clearance from theoretical volume distributions
(s.e.e. = 32.71 mi/mm, r = 0.97, p < 0.001) was obtained from
the 54-mm plasma sample. The equation best fitting our data is
C1EC
1454.21[1 —exp( —0.00457((ID/CM) —3.55))].
Eq. 3
The parameters of the equation for various sampling times
are presented in Tables 1 and 2.
DISCUSSION
In adults, several algorithms are available that allow estima
tion ofthe renal clearances of@Tc-MAG3
and OIH by means
of one blood sample that is obtained at 43 and 44 min after
THEJOURNAL
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Vol. 38 •
No. 11 November 1997
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A@Bm46.@:@4o
/
@:\
Vz
\,h@_/u@.
.
@
0
.
40
0
100
@Tc-ECclearance(m@nin)
Samping@O
time (mm)M@sampie
@
FIGURE1. Plotsofs.e.e. @c-EC
clearance
andtheoretical
volumedistributions
obtained
fromvarious
sampling
times.Theleasts.e.e.wasObtained
at 54mm.(B)Technetium-99m-EC
clearanceasmeasuredby mumpleplasmasamplemethod(ordinate)
andtheoreticalvolumeof distributionQD/C@)
at 54
mm (abscissa).(C) Correlationof clearancesbetween single-sample
@c-EC
clearanceObtainedfrom 54-mm plasma sample (abscissa)and reference
@“@Tc-EC
clearances (ordinate)(y = 13.379 + 0.9538x;r = 0.98).
@
injection, res@ectively (8,9). Similarly, results of this study
suggest that
Tc-EC clearance can be estimated from a single
plasma sample with an acceptable error of estimation for
routine clinical studies (s.e.e. 32.7 mllmin). The optimal sam
pling time is found to be 54 mm postinjection. The difference in
optimal sampling times between 9@Tc-EC and the other
tubular agents may be explained by the lower rate constants of
@“@Tc-EC
compared to those of 99mTc@MAG3 and OIH
(1,2,5,7).
The method based on the regression between a reference
clearance and the plasma concentration is population depen
dent, and the technique is feasible when a patient has the same
characteristics as the group of patients that the method is
derived from. The sampling time for the validity of the single
sample technique is a function of distribution volume and the
clearance and varies with every case rather than being a
constant time (1 1,12). Accordingly, with a different patient
population, Stoffel et al. (13) reported a different optimal
sampling time for 99mTc@EC(i.e., 80 mm after injection). The
sampling time for single plasma sample clearance determina
tions depends on the level of renal function. Low- and high
clearance rates require different plasma sampling times (12).
Plasma samples can be obtained closer to the time of injection
when the renal function is good, and longer times are required
when the renal function is poor. The optimal sampling time is
preferred when the renal function is not known. This study was
conducted in 72 patients with a wide range of renal function.
TABLE I
Values of Coefficients of the Exponential Formula and Standard
Error of Estimations of Regression
1@rTle
(mm)F@ (mVmin)a
Coef.
(liter1)Via@ Qiter)S.e.e(mVmin)Corr.
TABLE 2
Values of Coefficients of the Exponential Formula and Standard
Error of Estimationsof Regression
Time
(r)301 (mVmin)a Qiter1)
(mm)F@
Coef
V@
(mVmin)Corr.
QIter)S.e.e
6.175045.660.950351
15
129.740.01
.380.959401267.370.0077
193.080.0094
6.051941
5.745737.620.966451432.170.0058
4.818234.750.971651
2.481835.610.970701015.710.0050
161.390.0047
2.335038.100.96675901
2.276240.840.96080816.560.0055
.170.0053
2.176643.620.95585755.100.0057
.944446.340.949Volume
1
obtained between 35-mm to 45-mm
betweendistributions
65-mm towere
85-mmplasmasamples.and
The clearance of 99mTcEC ranged between 12 ml/min and 660
ml/min with a mean value of 275.5 ± 117.4 mL/min. The
optimal sampling time of 54 mm can be used in patients for
whom the renal function is not known.
CONCLUSION
This study presents a simplified single-sample method for
determination of @“@Tc-EC
clearance. Since the s.e.e. is not
different, the 50-mm sampling time can be also used for
practical purposes (Table 1). The s.e.e., with this formula,
seems to be within an acceptable range for most clinical studies.
This finding needs to be validated by a prospective study,
preferably with a continuous infusion
@Tc-ECclearance
determination.
(r)
ACKNOWLEDGMENTS
The authors thank Ferahi c@k@rand Maral Delda@ for their
501476.030.00504.126533.070.974511476.100.00483.980632.900.974521472.480.00483.835232.780.975531465.270.00463.690832.720.975541554.210
excellent assistance and their cooperation. We also thank Prof. W.
Newlon Tauxe for his help in data processing and analyzing and
Prof. Ali Tan I@itmanfor his help in preparationofthe manuscript.
This work was supported by the Research Fund of The University
1332.750.975561421
of Istanbul. Project no. 0-130/200995.
.070.00453.280232.840.975571399.390.00453.155432.980.974581374.900.00453.038733.180.974591347.920.00452.931633.420.974601318.960.00452.831633.700.973
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SINGLE-SAMPLE
I. Verbruggen AM, Nosco DL, Nerom VCG, Bormans GM, Adrians PJ, Dc Roo Mi.
Technetium-99m-L,L-ethylenedicysteine:
a renal imaging agent. I. Labeling and
evaluation in animals. J Nuci Med l993;20:738—746.
2. Van Nerom CG, Bormans GM, Dc Roo Mi, Verbruggen AM. First experience in
healthy volunteers with technetium-99m-L,L-ethylenedicysteine, a new renal imaging
agent. Eur J Nuci Med 1993;20:738—756.
3. Ozker K, Onsel
@,Kabasakal L, Ct al. A new technetium labeled renal agent
Tc-99m-ethylenedicysteine: a comparative renal scintigraphic study with Tc-99m-
TEC@-n@ETIuM-99m-EC
CLEARANCE
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et al.
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MAG3 and I-l31-OIH in patients with obstructive renal diseases. J Nuci Med
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4. Kabasakal L, Turoglu HT, Onsel C. et al. Comparative continuous infusion renal
clearance of Tc-99m-EC, Tc-99m-MAG3 and l-l3l-OIH. J Nuci Med l995;36:224—
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5. Kabasakal L, Atay 5, Vural AV, et al. Evaluation of technetium-99m-ethylenedicys
teine in renal disorders and determination of extraction ratio. J Nuci Med 1995;36:
1398—1403.
6. Kabasakal L, Ozker K, I@itmanAT, Onsel @.Relationship between the OIH and
Tc-99m-EC clearances. Nuci Med Commun l994;l5:1006—l007.
7. Surma
Mi, wiewio@
J, Liniecki
i. Usefulness
of Tc-99m-N,N-ethylene-l.dicysteine
complex for dynamic kidney investigations. Nuci Med Commun 1994;l5:628—635.
8. Tauxe WN, Dubovsky E, Kidd 7, Diaz F, Smith LR. New formulas for the calculation
of effective renal plasma flow. Eur J Nuc! Med l982;7:5l—54.
9. Russel CD, Taylor A, Eshima D. Estimation of technetium-99m-MAG3 plasma
clearance in adults from one or two blood samples. J Nuci Med l989;30:1955—1959.
10. Sapirstein LA, Vidt D, Mandel M, et al. Volumes of distribution and clearances of
intravenously injected creatinine in the dog. Am J Physiol l955;I8l:330—336.
I I. Chatterton BE. Limitations of the single sample tracer method for determining
glomerulat filtration rate. Br J Radio! 1978;5l :981—985.
12. Kotzerke i, Burchert W, Wiese H, Smekal U'V, Hundeshagen H. Limitations of
clearance determination using the single sample distribution volume method. Eur
JNuc!Med l992;l9:l9—24.
13. Stoffel M, iamar F, Van Nerom C, et al. Technetium-99m-L,L-ethylenedicysteine
clearance and correlation with iodine-125..orthoiodohippurate
for the determination of
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Technetium@99m-Tetrofo smin Uptake in Sarcoido si s
Stage I
Doris Tschabitscher, Hans Jürgen
Gallowitsch, Peter Mikosch, Ewald Kresnik, Iris Gomez, Mario Molnar, H.P. Dinges,
Alois Kroiss and Peter Lind
Departments ofNuclear Medicine and Special Endocrinology and Institute ofPathology, Landeskrankenhaus Klagenfurt,
Institute ofNuclear
Medicine,
Krankenanstalt
Rudolfst@flung, Vienna, Austria
The uptake of @“@Tc-tetrofosmin
in enlarged lymph nodes, of the
lung hilus, in the case of sarcoidosis Stage I (histopathologically
confirmed by mediastinoscopic biopsy) is demonstrated. On a
routine chest radiograph of a 78-yr-oki woman, hilar lymptiadenop
athy was first detected. In the following mammography, dissemi
CASE REPORT
In a 78-yr-old woman, who underwent a routine check-up, a
chest radiograph was taken and hilar adenopathy was first detected.
The subsequently performed mammography showed a region
(about 15 mm in diameter) with disseminated microcalcifications
in the left breast. To reveal possible breast cancer, a @mTc@
nated micro calcilications were found in the left breast and a
tetrofosmin
study was performed. For imaging, we used a double
@rc-tetrofosmin
study was performed for detection of breast
headed gamma camera with LEHR collimators. Five minutes after
cancer. Scintigraphy using
@‘Tc-tetrofosmin
showed clear uptake
in the hilar lymph nodes, but not in the left breast The
@Tc intravenous injection of 370 MBq 9@―Tc-tetrofosmin,three static
images were taken in prone position (right lateral, left lateral and
tetrofosmin uptake in the hilar lymph nodes was due to sarcoidosis
confirmed by histoiogy. Therefore, °@rc-tetrofosmin scintigraphy
anterior), followed by SPECT and three-dimensional reconstruc
may be useful in patients with suspected sarcoidosis, especially in tion 20 mm postinjection. All images showed an increased uptake
Stage I.
in the mediastinal cavity (Fig. 1). In the region ofthe left breast, no
Key Words technetium-99m-tetrofosmin; hilarlymphadenopathy; pathological uptake could be detected. Because of these findings,
sarcoidosis Stage I; SPECT
the patient underwent MRI ofthe chest and mediastinum. The images
showed a conglomerate of partially, but distinctly enlarged, mediasti
J NucI Med 1997;38:1786-1787
nal and hilar lymph nodes (Fig. 2). Other investigations, including
laboratory findings (full blood count, angiotensin-converting enzyme,
tumor markers, lymph cell typing), spirometry, ECG, sonography of
uncertain etiology. The diagnosis of pulmonary sarcoidosis is the neck and the abdomen,transmissionCT of the abdomenand bone
often established by exclusion. It is difficult to assess the marrow biopsy were all reported to be normal. Subsequent mediasti
activity of sarcoidosis by conventional clinical, radiological and noscopy with lymph node biopsy was performed. Pertaining to
physiological parameters as none of these are specific for the histology, the diagnosis sarcoidosis was confinned (Fig. 3).
inflammatory process. Gallium-67 scintigraphy is effective in
the detection of lesions not revealed by conventional methods
of investigation, particulary those affecting mediastinum (1—3). DISCUSSiON
Technetium-99m-tetrofosmin
is a lipophilic, cationic complex
Sarcoidosis is a systemic granulomatous disease of unknown
proposed for myocardial perfusion imaging. It has been found etiology. Uptake for 67Ga and JOOl macrophage targeting
that 9@Tc-tetrofosmin also has other useful applications espe
glycolipopeptide has been previously described in sarcoidosis
cially in oncology. Recent articles were able to demonstrate its by various authors (2,3, 11). In addition, only a few case reports
uptake in parathyroid adenomas (4), recurrence and distant on 201Tl and 9@Tc-sestamibi for imaging sarcoidosis are found
metastases of differentiated thyroid cancer (5—7)as well as in in the literature (12, 13). One article describes the uptake of
malignant breast tumors (8—10).
9@Tc-tetrofosmin in lung tumors (14), but not in sarcoidosis
We report a case ofpositive 99mTc..tetrofosminuptake in hilar (neither Stage I nor other stages). Technetium-99m-labeled tetro
lymphadenopathy in a case of sarcoidosis Stage I.
fosmin is a cationic, lipophilic radiopharmaceutical proposed for
myocardial imaging. The mechanism by which it concentrates in
tumor tissue was recently described by Arbab et al. (15). In our
ReceivedNov.21,1996;revisionacceptedFeb.24,1997.
For correspondence or reprints cont@t: Peter Und, MD, Department of Nuclear case, the images showed that capture ofthe tracer by the enlarged
Med@ine and Special Endocrinology, St. Veiterstra@e 47, A-9020 Kiagenfurt, Austha.
hilar lymph nodes was quite satisfactory, and it left the area of the
Sarcoidosis
isachronic
inflammatory
multisystem
disease
of
1786
THEJOURNAL
OFNUCLEAR
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•
Vol. 38 . No. 11 November 1997