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Rapid Assessment of 99MTc-Pertechnetate Uptake in the Knee Joint as a Parameter of Inflammatory Activity.

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348
RAPID ASSESSMENT OF
99mT~-PERTECHNETATE
UPTAKE IN
THE KNEE JOINT AS A PARAMETER
OF INFLAMMATORY ACTIVITY
A G N E S M. T H . BOERBOOMS and WIL C. A. M. BUYS
Shortly after intravenous injection of ""'Technetium-pertechnetate (99"'Tc04-)(200pCi), the activity
of the knee joints was studied in patients with clinical
arthritis of one or both knees and compared with that in
normal subjects. A rest period directly before the study
improved reproducibility. The values found shortly after
injection were comparable with measurements at the maxuptake in comimum. The significance of the g8"'T~04parison with the histologic findings in cases of doubtful
arthritis was examined.
A difficulty often encountered in the study of
various forms of arthritis is the lack of an objective
numerical measure of severity. The difficulty might be
overcome by a method which, unlike the frequently used
simple indirect methods that depend t o a variable extent
on extraarticular influences, gives direct information on
the severity of arthritis.
Dick et al. ( I ) demonstrated that maximum levels
of gg"'Tc04- uptake in the knee joint after intravenous
injection of e8mTc-pertechnetate (200 pCi) constitute a
From the Department of Medicine, University Hospital, Nijmegen, The Netherlands.
Agnes M.TH. Boerbooms. M.D.: Chief, Division of Rheumatology, Department of Medicine: Wil C.A.M. Buys: Physicist; Staff
Member of Internal Medicine, Department of Medicine.
Address reprint requests to Dr. A.M.Th. Boerbooms, St.
Radboud Hospital, Department of Internal Medicine, Division of
Rheumatology. Geert Grooteplein Zuid 16, Nijmegen. The Netherlands.
Submitted for publication August 18, 1977: accepted in revised form December 27, 1977.
Arthritis and Rheumatism, Vol. 21, No. 3 (April 1978)
valuable parameter of joint inflammation. They established a wide range in variation within a group of normal subjects and considerable overlap between normal
subjects and rheumatoid patients.
We made an investigation using the 8g"'T~-pertechnetate uptake described by Dick er al. ( 1 ) for determination of inflammatory activity in the knee joint as a
basic technique, which was further elaborated and modified. T h e apparatus used was checked before each examination with the aid of a 57C0source that has approximately the same energy spectrum as ggmTc,and a
correction on the dose injected was introduced. The
influence of exertion on the values measured was studied. The aim of this study was to establish whether
measurements taken shortly after g8"'Tc04-was injected
intravenously and measurements at the maximum
would give comparable results, because it is important
t o the subject examined as well as to the investigator to
minimize the duration of the examination. The
g g m T ~ 0 uptake
4and other parameters of activity of
joint inflammation, such as warmth, swelling, pain, and
hydrops, were compared. In patients with n o definite
evidence of arthritis the diagnostic significance of
9g"'T~04uptake in the knee joint was studied and compared with the histologic findings.
MATERIAL AND METHODS
Subjects. Studies were performed o n f o u r g r o u p s of
persons. T h e first consisted o f 22 patients, 14 females a n d 8
males, m e a n a g e 42 years (range: 18-65), with clinical evidence
ASSESSMENT OF ""Tc-PERTECHNETATE
of monoarticular arthritis. A joint was considered clinically
inflamed if at least warmth or swelling could be established by
palpation. The second group consisted of 24 subjects, 15 females and 9 males, mean age 47 years (range: 20-70). with
clinical evidence of bilateral arthritis. The third was the control group which consisted of 23 healthy volunteers, 15 females
and 8 males, mean age of 34 years (range: 19-54). The fourth
group consisted of 8 females and 3 males, whose ages ranged
from 18 to 66 years, with complaints of pain in the knee joint,
but with no definite clinical evidence of warmth or swelling. In
0 4 - in
this group the diagnostic significance of D D m T ~ uptake
the joint was investigated by comparison with the histologic
findings in the synovial biopsy.
Methods. One hour before and during the examination, the subject rested on a couch with both legs horizontal at
an angle of 40 degrees supported on the lateral side of both
legs by sand bags, which prevented leg movements. The room
temperature varied on different days from 23 to 25°C. Two
collimated thallium-activated sodium iodide crystals were used
to detect the y-radiation of the ""T
'c
in the knee joint as a
function of time after injection. These collimators (height 18.5
cm and diameter I 1 cm) were vertically positioned in the
center of the patella, touching the skin. Before each examination the apparatus was checked with the aid of a 5'C0 source.
Approximately 200 pCi (standardized by count rate) B B m T ~ 0 4 in 10 ml 0.9% NaCl was quickly (within 5 seconds) administered intravenously into a vein in the anticubital fossa, and
counts per 30 seconds were taken during 30 minutes. The
measurements shortly after injection (2% minutes) and at the
maximum (20-30 minutes) were converted to cpm/pCi injected.
All patients were questioned and examined by one
investigator (Boerbooms) with special attention to the manifestations of gonarthritis: pain, swelling, redness, or a history
of pain or swelling of the knee joint. The clinical activity of the
knee joint inflammation was assessed by palpation. Tenderness and warmth, both measured over the medial articular
space, as well as swelling and hydrops were classified in arbitrary categories of increasing activity (0 to 3). For the measurements of tenderness and warmth (the latter measured with
the dorsum of the hand) the medial articular space was chosen
because it is important for comparison to always measure at
the same location and at a place as near as possible to the
Table 1. 99n'Tc-PertechnetateUptake of the Knee Joints after
Intracenous Injection oJ200 WCi in 5 Healthy Controls with and without
a One-Hour Rest
2% Minutes
(cpm/pCi)
Maximum
(cpm/ctCi)
48.5
7.0
66.0
9.0
71.5
6.0
86.5
8.2
17.7
8.8
15.0
Mean uptake with one hour rest
SD
Mean uptake without one hour rest
SD
Mean differences with and without rest
SD o f the differences
Significance
P
< 0.05
4.2
P
< 0.01
349
1
23/4 min
mona r t icu l a r
bilateral
arthritis
arthritiz
normal normal ]arthritis
Pw=O,67
I
,Pw < 0,0001 (A*C)
20c
180
60
40
20
00
80
60
40
C
D
Figure 1. ee"Tc-pertechnetate uptake ofthe knee joints, 2% minutes aster intravenous injection ofZGOpCi, in 23 healthy controls,
22 patients with nionoarticular. and 24 with bilateral arthritis.
Open circles refir to knee joints, which developed clinical arthritis within one year. Pw = 0.67 ( A ++ B ) ; Pw < O.ooO1 ( A C);
Pw < 0.0001 ( A
D ) . Pw = tail probability of Wilcoxon's two
sample test.
--
-
synovium. The choice of the medial articular space instead of
the lateral space was arbitrary.
The synovial biopsy, obtained under direct vision by
arthroscopy of the knee joint, was examined by light microscopy. The vascular alterations, that is, microscopically demonstrable vascular proliferation, vasodilatation, and cellular infiltration, were examined. These pathologic findings were
classified in four categories: 0 = normal; I = slight: 2 =
moderate and 3 = severe alterations.
BOERBOOMS AND BUYS
3 50
Table 2. Reproducibility of @@"TcO.-Uptake in 28 Knees of Controls
RESULTS
Exertion before the radioisotope injection influenced the height of the values measured (Table 1). The
8 8 m T ~ 0 4uptake
after exertion was significantly higher
than that after a rest period of one hour (Student's t test
of paired data). In view of this, a rest period of an
arbitrarily fixed duration of one hour was introduced
,Pw <O,OOOl(A-C),
Pw-<O,O
220 200 180 -
160140-
12010000.
.w..---.
..o
-----
80-&
.
----m
eenn8e.
60-
l
e
C
A
D
Figure 2. @Om Tc-pertechnetate uptake of the knee joints. at the
maximum after intravenous injection of 200 pCi, in 23 healthy
controls, I9 patienis with monoarticular. and 24 with bilateral
arthritis. Open circles refer to knee joints. which developed clinical arthritis within one year. Pw = 0.68 ( A - B ) ; Pw < 0.0001 ( A
C ) ; Pw < 0.0001 ( A D). P w = tailprobability of Wilcoxon's
two sample test.
-
-
Mean
Duplicate SD
Relative duplicate SD
59.3
2t
56.6
4.0
6.8%
Maximum
(cpm/rCi)
I*
79.0
2t
78.7
3.4
4.4%
1 = first occasion.
t2
P~=0,68
I
I*
*
maximum
I
I
2% Minutes
(cpm/pCi)
=
second occasion.
immediately before each examination. In 23 healthy
controls (46 knees) the standard deviation of the measurements at various intervals after 8 8 m T ~ 0 ,injection
proved to be practically the same. There was a considerable variation of the 8 8 m T ~ 0 , -uptake in the knee
joints within the group of normal subjects (Figures 1
and 2). Correlation with age, sex, height, weight, and
knee circumference could not be established. The reproducibility of the method that was studied in 14 normal
subjects after introduction of a rest period of one hour
was good. The relative duplicate standard deviation
of the differences between the values found in these two
examinations was 6.8% for the 2% minute uptake and
4.4% for the maximum. (Table 2). The time interval
between the first and the second examination varied
from 4 days to 3 months.
Comparison of the values measured for the knee
joints of normal persons with those for clinically inflamed knee joints in patients with monoarticular and
bilateral arthritis disclosed a highly significant difference. Maximum normal values accepted for 2% minutes
and plateau were 70 cpm/pCi and 90 cpm/pCi g 8 m T ~ 0 4 - ,
respectively (Figures 1 and 2). There was a correlation
4in the knee joint 2% minbetween the 8 8 m T ~ 0uptake
and
utes after intravenous injection of 200 pCi s8mT~0,that at the maximum (Figure 3). There was a very good
correlation between the results of the 88mTc-pertechnetate study and the degree of warmth over the
medial articular space. The correlation with spontaneous pain and swelling was more doubtful, and there was
no correlation with the degree of tenderness and with
hydrops. In 11 patients with complaints of pain in the
knee but with no definite evidence of warmth and/or
4in the knee joint 2% minswelling, the g 8 m T ~ 0uptake
utes after injection and at the maximum were compared
with the histologic findings in the synovial biopsy (Table
3). When an increased severity of hyperemia was found,
the 8 8 m T ~ 0 4uptake
was also increased.
ASSESSMENT OF gg"'T~-PERTECHNETATE
35 1
technetate was the simplicity of administration: intravenous injection versus intraarticular administration of
lS3Xe.The main advantage of external direct counting
210 over the joints in comparison with scintiphotography of
the joints is the lower dosage of g9mTc;quantitation was
190 less difficult and the distribution of the radionuclide in
the joint seen on the photoscan is not relevant for our
170 study.
The measuring methods using radionuclides
150 probably reflect above all the vascular changes (vascular
1 30 proliferation, vasodilatation, vascular congestion, and
endothelial lesions), which are an essential feature of the
110synovial inflammatory reaction. We suppose that the
endothelial lesions also contribute to an increased
90 . 89%
I
g 9 m T ~ 0 uptake
4in the knee joint shortly after injection
normal right
because
we
found
a small amount of radioactivity
7c
o normal l e f t
already
in
a
sample
of synovial fluid withdrawn one
A bilateral right
A bilateral left
minute after intravenous injection (4). Some authors
50
I
( 5 - 8 ) maintain that the vascular changes in synovitis
30
50
70
90
110 130 150 170 190 210
appear in an early stage of chronic polyarthritis.
2 % min ( c p m / p C i )
There are various opinions about the optimal
Figure 3. Comparison between ihe 88"'Tc0,-uptake in the knee joint 2%
time of measuring the inflamed joints with ggmT~-perminutes and on the nraxiniutn aster intravenous injection of 200 pCi
technetate. Dick et al. counted 15 minutes after injection
TeO; in 23 normal persons and 21 patients with a bilateral arthritis.
(9)
and found that this time was acceptable. We found
The correlaiion coeficient is 0.98; P < 0.001.
that there was a significant difference between the
9 9 m T ~ 0uptake
4in the inflamed knee joint and that in
DISCUSSION
the normal joint at any time shortly after injection as
well as at the maximum. Although a rapid increase in
Several authors have suggested the possibility of
wmTc-pertechnetateuptake measured over the knee ocobtaining exactly measurable data on arthritis with the
curred in particular during the first 5 minutes, the stanaid of radionuclides such as 133xenon(2) and gemtechdard deviation for the measurements at various intervals
netium-pertechnetate ( 1 , 3).
after
injection proved to be practically the same. This
The main reason for choosing ggmT~-perobservation agrees with the conclusion of Hays and
Green (10) that scanning every moment until 40 minutes
Table 3. 99"Tc04- Uptake and Synovial Microscopy in I 1 Patients
after injection affords the best chance of detecting signifwith Pain and Clinically Doubtful Arthritis ( Hyperemia and Cellular
icant differences. We opted for measuring very shortly
Injiltrate Scores 0-3)
after injection because it is important to the subject
99m~C0~Microscopy
examined as well as to the investigator to minimize the
duration of the examination. An excellent correlation
Subject
2% Minutes Maximum
Cellular
was found between the results of the ggmTc-pertechnetate
Number
(cpm/FCi) (cpm/pCi) Hyperemia
Infiltrate
study and the degree of warmth over the medial articuI
45.2
ND
0
0
lar space (4).The correlation with spontaneous pain and
2
75.8
49.9
0
0
swelling scores was good. Paterson et al. ( 1 1 ) also ob62.3
3
0
0
53.1
tained a good correlation between pain scores and
4
ND
63.8
0
I
9
9 m T ~ 0 4Deodhar
-.
et al. (1 2) also found a good correla5
69.3
89.8
0
2
tion between ggmTcO,- uptake and the knee scores of
6
75.1
ND
I
I
7
81.4
102
I
2
joint inflammation.
108.6
8
88. I
2
I
In the synovial biopsy from patients with com9
72. I
103.2
2
I
plaints
of the knee joint in the absence of clinical symp10
126.1
97. I
1
2
toms,
we
observed histologic evidence of inflammation
II
116.5
130.9
2
1
and an increase of 9 9 m T ~ 0 ,uptake.
This investigation
maximum (cpm/pc i)
230 -
I
.
BOERBOOMS AND BUYS
352
G . Gordon I, Whaley K, Boyle JA, Buchanan WW: Derishowed that the 89mTc-pertechnetateuptake is a more
vation of knee joint synovial perfusion. Ann Rheum Dis
sensitive tool in diagnosing inflammation than the clini29, 131-134, 1970
cal parameters of warmth and swelling. Two of the 23
3.
McCarty DJ, Poleyn RE, Collins PA: e e m T e ~ h n e t i ~ m
normal subjects developed (Figures 1 and 2, open cirscintiphotography in arthritis. I . Technic and intercles) clinical signs of arthritis of the knee joints within a
pretation. Arthritis Rheum 13:l I , 1970
year after the g 9 m T ~ 0 examination.
4It is possible that
4. Boerbooms AMTh: Het meten van de ontstekingsactivithe positive g g m T ~ 0uptake
4was an early sign of inteit in het kniegewricht met behulp van eemT~-perflammation.
technetaat. M.D. Thesis, 1975, Nijmegen
Radioisotope uptake studies of the knee joint
5. Kulka JP: Vascular derangements i n rheumatoid arthritis,
with the aid of ggmTc-pertechnetategive an objective
Modern Trends in Rheumatology. Edited by AGS Hill.
London, Butterworths, 1966, pp 49-70
quantitative and fairly reproducible parameter of pos6. Schumacher HR, Kitridov RC: Synovitis of recent onset.
sible inflammatory activity, even if restricted to shortArthritis Rheum 15:465-485, 1972
term measurements a few minutes after injection of the
7. Pathologie Rheumatischer Erkrankungen. Edited by H G
radionuclide used. If the proper equipment is available
Fassbender. Berlin, Heidelberg, New York, Springer Verg g m T ~ 0uptake
4studies of the knee joint are relatively
lag, 1975, p p 87, 169-171
simple and inexpensive. Also the radiation load is very
8. Sokoloff L: The sternoclavicular articulation in rheumatic
small. I n our opinion the indications for 9 g m T ~ 0 4 diseases. Am J Clin Pathol 24:406-414, 1954
uptake studies of the knee joints and probably also of
9. Dick WC, Grennan DM: Radioisotopes in the study of
other joints are that the B g m T ~ 0uptake
4technique can
normal and inflamed joints. Clinics in Rheumatic Disbe useful i n the diagnosis of doubtful arthritis and in
eases. Edited by MIV Jayson. London, Philadelphia, Toclinical research, such as for determination of the effect
ronto. Saunders Company, 1976, 2, pp 67-76
10. Hays MT. Green FA: The pertechnetate jointscan. 1. Timof local and systemic therapy in inflammatory activity
ing. Ann Rheum Dis 31:272-277, 1972
in the knee joint.
1 1 . Paterson J, Watson W, Teasdale E, Newman P, James W,
REFERENCES
1. Dick WC, Neufeld RR, Prentice AG, Woodburn A, Wha-
ley, K , Nuki G, Buchanan WW: Measurement of joint
inflammation. A radioisotope method. Ann Rheum Dis
29. 135-137, 1970
2. Dick WC, Onge St RA. Gillespie FC, Downie WW, Nuki
Pitkeathly DA: Assessment of rheumatoid inflammation
in the knee joint: a reappraisal. Ann Rheum Dis 36:288,
I976
12. Deodhar SD, Dick WC, Hodgkinson R, Buchanan WW:
Measurement of clinical response to antiinflammatory
drug therapy in rheumatoid arthritis. Quart J Med ns 42
166:387-401, 1973
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