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9

Review

The Scintigraphic Donald

Diagnosis

of Osteomyelitis

S. Schauwecker1

Osteomyelitis is a serious health problem that results in multipie limb amputations annually. This article reviews the current scintigraphic procedures used in the diagnosis of osteomyelitis and

Article

discusses

some

of

the

being developed. The goal weaknesses of each method

newer

radiopharmaceuticals

the bone scan will show abnormal uptake of the radionuclide 1 0-1 4 days before loss of bone mineral is great enough to be seen on plain radiographs [4]. For example, 17 of 19 sites of osteomyelitis in children that were imaged within 3 days after the onset of symptoms showed abnormal uptake on the bone scan, whereas only one abnormal site was seen on the radiograph [5]. In fact, if antibiotic therapy is begun early enough to arrest the loss of bone mineral, the characteristic radiographic findings may never develop [6]. The three-phase bone scan is the routine nuclear medicine procedure for diagnosis of osteomyelitis. The first phase, the nuclear angiogram or flow phase, consists of serial 2- to 5sec images of the area of suspected osteomyelitis that are obtained during injection of the radiopharmaceutical. The second phase, the blood-pool image, is obtained within 5 mm after injection. In areas of inflammation, capillaries dilate, causing increased blood flow and blood pooling. The third phase, the bone image, is obtained about 3 hr later, when urinary excretion has decreased the amount of the radionuclide in the soft tissues. Classically, with cellulitis, diffuse increased uptake occurs in the first two phases, but uptake is normal or diffusely increased in the third phase (Fig. 1). If present, diffuse increased uptake in the third phase is probably due to regional hyperemia caused by the cellulitis [7] (Fig. 1). Osteomyelitis causes focally increased uptake in all three phases (Fig. 2). Recently, some have proposed adding a 24-hr image to the three-phase bone scan to create the four-phase bone scan [8, 9]. The amount of radionuclide in the lesion vs the amount in normal bone should continue to increase during the fourth

now

is to understand the strengths and so that the procedure most effective

for specific clinical settings can be selected. In general, the threephase bone scan is the procedure of choice if the suspected osteomyelitis is not superimposed on another disease that causes increased bone remodeling (i.e, findings on the radiograph are normal). If the suspected osteomyelitis is superimposed on a disease that causes increased bone remodeling, the combined 1111n-labeled Ieukocyte-”Tc bone scan is the procedure of choice in the non-marrow-containing skeleton and the 1111n-labeled leukocyte and mTc bone marrow scans are the procedures of choice in the marrow-containing skeleton.

Use of scintigraphy in the diagnosis of osteomyelitis was established in 1975 when three landmark articles [1-3] appeared. First, Duszynski et al. [1] discovered that a bone scan could be used to diagnose osteomyelitis several days before radiographs showed any abnormalities. Second, Gilday et al. [2] added the blood-pool image to the bone image as a forerunner of the current three-phase bone scan. Finally, Deysine et al. [3] proposed the use of gallium-67 for the study of chronic and postoperative osteomyelitis.

Three-Phase

Bone Scan

Localization of 99mTc-diphosphonate both osteoblastic activity and skeletal

in bone vascularity.

is related to Commonly,

Received April 19, 1 991 ; accepted after revision July 1 9, 1991. This work was supported in part by National Institutes of Health grant AR 36460. 1 Department of Nuclear Medicine, Indiana University School of Medicine, Wishard requests to D. S. Schauwecker. AJR 158:9-18,

January

1992 0361 -803X/92/1

581-0018

© American

Roentgen

Memorial

Ray Society

Hospital,

1 001 W. 1 0th St.

,

Indianapolis,

IN 46202.

Address

reprint

SCHAUWECKER

10

AJA:158,

January

1992

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#{182} .

.

1L1

,.;.

,.

B

A

C

in plantar projection shows classic findings of cellulitis. show diffuse increased blood flow to right medial forefoot. uptake of radionuclide in blood pool throughout right foot, especially C, Delayed image shows no area of focal increased activity corresponding to findings of first two phases right foot compared with left foot is caused by hyperemia from cellulitis [7]. Fig. 1.-Three-phase

bone

scan

A, Four frames from dynamic phase B, Second phase shows increased

A

B

Fig. 2.-A-C, Three-phase bone scan shows intense focal localization in left fifth metatarsal.

phase, if the lesion is osteomyelitis bone scan is based on solid theoretical of ggmTcmethylene

diphosphonate

lamellar bone (normal skeleton)

classic

stops

findings

of osteomyelitis.

at about

4 hr in

for about 24 hr

in woven bone (abnormal bone around osteomyelitis and bone tumors) [9]. The four-phase bone scan has proved useful for the evaluation of lesions of the feet in patients with peripheral vascular disease [8]. Often, bone detail is very poor on 3-hr

delayed images in these patients, but is greatly improved by 24 hr. To date, the four-phase bone scan has not been widely accepted, perhaps because of the inconvenience of having the patient return for the fourth phase. False-positive results have been reported for degenerative diseases [8] and metas-

tases [9]. Guan et al. [1 0] reported 4-hr uptake ratio can be used malignant bone lesions.

that the increased

to differentiate

right

medial forefoot area shown in A. increased activity throughout

C

[8, 9]. The four-phase considerations. Uptake

but continues

in same

(A and B). Diffuse

benign

24-hr/ from

Flow images

(A),

blood-pool

image

(B),

and delayed

image

(C) all show

In adults who have normal findings on radiographs (i.e., who have no lesions that cause increased bone turnover), the three-phase bone scan has high sensitivity and specificity (Table 1). When the results in Table 1 are added together, sensitivity is 94% (1 82/1 94) and specificity is 95% (360/380). In routine clinical practice, most cases of osteomyelitis can be detected by using the three-phase bone scan. In neonates, the sensitivity of the three-phase bone scan

decreases.

Neonates

with osteomyelitis

or cold defects on three-phase bone time [14-16]. There are two possible explanations

these

studies

were

performed

have falsely scans

22-68%

for these

results.

in the late 1970s;

normal of the First,

gamma

cameras have improved since then. More recently, Bressler et al. [1 7] studied 33 neonates less than 6 weeks old, and 13 (87%) of 1 5 had classical findings for osteomyelitis on three-

AJR:158,

January

TABLE Optimal

1: Results Conditions

SCINTIGRAPHY

1992

of Three-Phase

Bone Scans

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Note-NA

phase

55/62 22/23 [1 1

]

1 6/1 7

21/23

7/8

NA 80/85

12/13

not available.

=

bone

scans.

The remaining

defects. The authors stressed quality scintigrams of the region

Second,

65/65 152/165 42/42

Allwright

two

patients

the importance of the epiphysis.

had cold of optimal-

for the second

study [19]. This does not

necessarily mean that 67Ga-citrate is more sensitive for neonatal osteomyelitis than the three-phase bone scan is. After further evolution of the lesion, the second study would more likely be diagnostic. The three-phase bone scan is less specific when bone remodeling is increased (Table 2). When the results in Table

2 are added together,

sensitivity

ificity is 33% (1 1 0/330). 111n-Iabeled leukocytes specificity. 1

is 95% (250/262)

and spec-

In these situations 67Ga-citrate or have been used to try to increase

Gallium-67

localizes

in areas of osteomyelitis

by granulocyte

or

bacterial infection

uptake, and by binding to lactoferrin at the site of [40]. However, 67Ga-citrate was originally proposed as a bone scanning agent [41 ], and it shows increased uptake in areas of increased bone remodeling, such as bones with

neuropathic

changes

To overcome

this

[42, 43] or pseudarthrosis problem,

some

[32] (Fig. 3).

authors

have

proposed

comparing the 67Ga-citrate uptake in the lesion with the uptake on a bone scan; disparate distribution of uptake or increased intensity would constitute osteomyelitis [44, 45]. Unfortunately, as seen in Table 3, 67Ga-citrate can be sensitive or specific in complicating cases, but it is difficult to obtain high sensitivity and high specificity simultaneously [28]. When

67Ga-citrate and 111n-labeled leukocytes have been directly compared in the same patient, the labeled leukocytes are usually

significantly

better

[28, 37, 38]. Currently, diagnosis available.

Reference

Sensitivity

Specificity

20/24

Modic et al. [21 ] Lewin et al. [22] Maurer et al. [23] Unger et al. [24] Sugarman [25] Magnuson et al. [26] Splittgerber et al. [27] Schauwecker et al. [28] AI-Sheikh et al. [29] Ivancevic et al. [30] Ruther et al. [31] Hadjipavlou et al. [32] Keenan et al. [33]

20/22

9/12 11/14 13/23 5/9

TABLE

of osteomyelitis

for the diagnosis

67Ga-citrate when

of osteomyelitis

is rarely

11n-labeled

used leukocytes

for the are

3: Results

5/8 3/4 9/1 1

of 67Ga-Citrate

Reference Lisbona Shafer Esterhai Merkel Al-Sheikh Modic Lewin

and Rosenthall et al. [34j et al. [351 et al. [361

13/20

37/37 50/50 3/3 32/32

30/95 9/48 0/3 0/25

10/10

3/12

15/1 5

0/2

13/13

0/19

2/2 31/31

0/9 17/39

et al. [29] et al. [21] et al. [22]

Indium-i

=

Scans

in Osteomyelitis

Sensitivity [1 1 J

Sugarman [25] Seabold et al. [37] Schauwecker et al. [281 Ivancevic et al. [30] Handmaker and Giammona [19] Merkel et al. [381 Hadjipavlou et al. [32] Borman et al. [39] Note-NA

Results of studies evaluating the sensitivity and specificity of 67Ga-citrate scans in osteomyelitis are variable (Table 3). When the results of these studies are added together, sensitivity is 81 % (209/257) and specificity is 69% (1 88/272). 67Ga-

citrate

in Osteomyelitis:

et al. [1 8] found that the cold lesion on

the third phase of the bone scan was caused by a subperiosteal abscess. In children, a large portion of the blood supply to the bone comes from periosteal vessels, and these are apparently disrupted by the subperiosteal abscess [1 8]. When clinical findings strongly suggest osteomyelitis, but findings on the three-phase bone scan are normal, 67Ga-citrate has

been recommended

Bone Scans

Park et al. [20]

Specificity

70/71

Gilday et al. [2] Howie et al. [5] Majd and Frankel [6] Lisbona and Rosenthall Kolyvas et al. [1 2] Maurer et al. [13]

11

OSTEOMYELITIS

TABLE 2: Results of Three-Phase Complicating Conditions

in Osteomyelitis:

Sensitivity

Aeference

OF

Specificity

17/1 7

23/23

1 5/1 6

21/22

13/1 3 1 1/23 8/10

0/11 6/7 10/12

12/13

7/7

8/8 25/26 2/9

16/23 15/50 16/16

21/21

2/8

12/1 5

2/2

13/1 7

NA

19/35

2/2 31/32

70/80 0/9 0/2

not available.

1 1-Labeled

Leukocytes

Leukocytes labeled with 1In have been used to overcome certain limitations of the 67Ga-citrate scan. Labeled leukocytes accumulate in areas of infection. Localization of the cells is specific for infection when suspected osteomyelitis is superimposed on processes that cause increased bone remodeling [23, 28, 46, 47]. The sensitivity and specificity of 11n-labeled leukocyte scans are reviewed in Table 4. When the results are added together, sensitivity is 88% (422/480) and specificity is 85% (389/457). Most of the reported studies of 1In-labeled leukocyte scintigrams are retrospective. Studies by Seabold et al. [37] and Esterhai et al. [49] are particularly important as they are prospective studies that used 1ln-labeled leukocytes to evaluate osteomyelitis complicating fracture nonunion. Their gold standard was open biopsy and culture in all patients. Esterhai et al. [49] had 1 5 true-positive findings and five true-negative findings. Seabold et al. [37] reported 1 6 true-positive, 28 truenegative, one false-positive, and three false-negative results. Together, these prospective studies had a combined sensitiv-

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12

SCHAUWECKER

AJR:158,

Fig. 3.-Neuropathic osteopathy can be difficult to differentiate from osteomyelitis. region on all three phases. A, Bone Image of three-phase bone scan shows increased uptake of radionuclide B, ‘TGa-citrate Image on day 5 is virtually identical to delayed bone image (A).

C, 24-hr “In-labeled leukocyte grafted, and foot healed normally.

TABLE 4: Results Osteomyelitis

study shows no accumulation

of 1111n-Labeled

Sensitivity

Reference

Schauwecker et al. [28] Merkel et al. [36] Ouzounian et al. [48] Wukich et al. [47] Esterhai et al. [49] lIes et al. [50] Magnuson Seabold

et al.

[26]

et al. [37] Al-Sheikh et al. [29] Maurer et al. [2318 Splittgerber et al. [2T] Schauwecker McCarthy Schauwecker

et al. [51 et al. [52] [53]

ja

Mulamba et al. [54] Keenan et al. [33]$ a

Diabetic

Leukocyte

Scans

in

Specificity

24/32 19/23 13/1 4 20/21 10/1 0 16/1 9

24/25 6/7 39/41 11/29 5/5 27/33

44/50

35/48

16/1 9 8/1 0 3/4 3/3

28/29 9/12 8/9 3/3

1 7/1 7 27/28 1 79/206

of radionuclide.

15/18 9/11 140/151

12/1 3

17/17

1 1/1 1

13/19

foot.

ity of9l % and specificity of97% complicating fracture nonunion.

in tarsal

for diagnosis

of osteomyelitis

in diabetics appear promising (Table 4), important still exist. Determining that infection is either present does not always answer all the clinical questions.

bone

cyte collection

al. [23] found that 111ln-labeled leukocyte scintigraphy had good sensitivity and specificity for the detection of infection in diabetic foot disease, but the scans were not useful for differentiating infection in the bone from that in the adjacent soft tissue. More recent work uses the combined “Tc bone 1ln-labeled leukocyte study to determine if the leuko-

showed

focal

increased

activity

in tarsal

of osteomyelitis

was seen. An ulcer was skin

is in the bone or soft tissue

(Figs. 4 and 5).

Using this combined study, Schauwecker et al. [51 ] correctly localized the infection to the bone or soft tissue 89% of the time in patients with neuropathic foot diseases. Unfortunately, even with these advances, the diagnosis of osteomyelitis superimposed on diabetic neuropathic osteopathy remains a challenging clinical problem. Seabold et al. [55] found that rapidly progressing noninfected neuropathic osteoarthropathy of recent onset can be indistinguishable from osteomyelitis with either the combined 99mTc bone scan111In-labeled leukocyte study or MR imaging.

One study [53] retrospectively

reviewed

485 patients

with

suspected osteomyelitis and showed some of the limitations of using 11n-labeled leukocytes. Acute osteomyelitis can be readily diagnosed anywhere in the body, whereas chronic osteomyelitis, with its lower influx of labeled leukocytes, is seen accurately in the peripheral skeleton only. The 11nlabeled leukocytes accumulate in active bone marrow, which

the sensitivity

for detection

of chronic

osteomyelitis

in the central skeleton [53]. Low sensitivity for vertebral osteomyelitis when using labeled leukocytes has also been reported by Whalen et al. [56] and Ruther et al. [31].

A cold defect

difficulties or absent Maurer et

scan

1992

region.

At surgery, no evidence

reduces

The diagnosis of osteomyelitis in patients with diabetic osteopathy is a serious clinical problem. Although the results

1

Three-phase

January

in the central

skeleton

on a

1ln-labeled

leukocyte study is often confusing (Fig. 6). The defect occurs in 1 0-40% of such studies for suspected osteomyelitis in the central skeleton [53, 56-59]. Although the cold defect could represent osteomyelitis, it also is seen in metastases, fractures, Paget disease, surgical defects, and intervals after irradiation [53, 56-59]. The cold defect is consistent with, but

not diagnostic serial studies

of, osteomyelitis. Palestro et al. [60] performed in patients with vertebral osteomyelitis and

found a progression from hot to cold as the lesions became more chronic. Whalen et al. [56] showed that antibiotic therapy was correlated with a high incidence of cold defects.

AJR:158,

January

SCINTIGRAPHY

1992

13

OF OSTEOMYELITIS

Fig. 4.-A-F, Combined three-phase bone scan-”ln-labeled leukocyte study for diagnosis of osteomyelitis in

a patient with obvious cellulitis. Images

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A

B = C and 0 + E = F. A and B, Left lateral 1111n-labeled leukocyte scan (A) and bone image (B). 0 and E, Plantar 1111n-labeled leukocyte scan (0) and bone image (E). C and F, Superimpositions of A on B (C) and 0 on E (F), respectively. 111lnlabeled leukocyte activity is localized to ventral and dorsal soft tissues and not within bone. This represents cellulitis without evidence of osteomyelitis. +

Fig. 5.-A-F, Combined three-phase bone scan-’111n-labeled leukocyte study for diagnosis of osteomyelitis. lmagesA +B=CandD+E=F. A and B, Plantar ‘11ln-labeled leukocyte scan (A) and bone image (B). D and E, Left lateral ‘111n-labeled leukocyte scan (0) and bone image (E). C and F, Superimpositions of A on B (C) and D on E (F), respectively. On both projections, activity clearly lies within, and adjacent to, bone. Osteomyelitis and adjacent cellulitis are clearly present.

L

.

41’ L

--

I

*_‘

#{149}

#{149}

,

C

V

.

.

.

..1...:’4#{149}....

#{149}

I#{149}

D Either of these mechanisms could result in a more indolent infection with decreased leukocyte accumulation. One way to improve specificity in the central skeleton is to perform a 99mTc bone marrow scan In-labeled leukocyte

E

.

F

study [61 -63]. The 99mTc sulfur or antimony colloid will clearly delineate the extent of the bone marrow. Any incongruity of the bone marrow and 1111n-labeled leukocyte images would be considered significant (Fig 7). Recently, this study has

14

SCHAUWECKER

been found complicating

to increase both the sensitivity and specificity for osteomyelitis in the central skeleton [64]. Thus,

the “Tc bone marrow scan and 111InIabeled leukocyte study are the procedures of choice for diagnosing complicating Downloaded from www.ajronline.org by 41.190.167.235 on 11/08/15 from IP address 41.190.167.235. Copyright ARRS. For personal use only; all rights reserved

osteomyelitis

in the marrow-containing

skeleton.

AJR:158,

False-positive

and

false-negative

results

of

January

1992

1In-labeled

leukocyte studies have multiple causes. Some authors have suggested that antibiotic therapy may lower the sensitivity of the 1111n-labeled leukocyte study [56]. Other authors [65, 66] have found no significant antibiotic effect. False-positive resuits have been reported with rheumatoid arthritis [67], healing fractures [68, 69], noninfected prosthesis [70], and metastatic carcinoma [53, 71 ]. Abreu [72] recently reviewed the literature and listed many causes of skeletal uptake of 11n-

labeled leukocytes. Usually the processes that give falsepositive results for infection have fainter accumulation of labeled leukocytes than is seen with osteomyelitis. The clinician often myelitis superimposed 1 1

is asked to diagnose on healing fractures.

11n-labeled leukocytes

first

month

but were

accumulated seen

only

suspected In a canine

appreciably

faintly

when

osteomodel,

during

the dogs

the were

imaged later [73]. This finding appears to agree with the results of Van Nostrand et al. [69]. A healing fracture should have faint uptake and be seen for only a few weeks after injury,

Fig. 6.-1111n-labeled leukocyte study shows a cold defect at L5, with normal distribution of labeled leukocytes in liver, spleen, and bone marrow. This study was consistent with, but not diagnostic of, osteomyelitis.

compared

with fracture

complicated

with osteomyelitis.

Other Radiopharmaceuticals 1ln is a 3+ cation that binds to transferrin 1 1

similarly to 67Ga-citrate

in solution.

However,

and behaves

some differences

-.

I

T:

‘

“4

a

.

:

______

H:.i

W:if.:.:

#{149}#{149};

.

‘a,,,

4.

,.‘...

F:.,

.

.‘

‘

A

B -

. -#{149}

.e

4

.

IJ..

.

.

P

.‘

L.

.

.I#{149}’’(

..

:

-D

Fig. 7.-67-year-old man had bilateral total knee replacements and suspected infection. A and B, Anterior (A) and right lateral (B) ‘lnlabeled leukocyte images show uptake of radionuclide around both knees. C and 0, Anterior (C) and right lateral (0) ““Tcsulfur colloid bone marrow images are essentially identical to A and B. This is consistent with normal bone marrow only, without evidence of infection.

AJR:158,

January

SCINTIGRAPHY

1992

OF OSTEOMYELITIS

occur. In is localized in the bone marrow, and 67Ga-citrate is incorporated into the bone. The exact mechanism for localization of 1ln-labeled leukocytes in osteomyelitis is not

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known.

When

the results

of Sayle

et al. [74, 75] and lies et

al. [50] are added together, sensitivity is 92% (1 09/1 1 9) and specificity is 81 % (42/52). To date, 11n has not had general acceptance, possibly because it is not an approved radiopharmaceutical

in the United

States.

Vorne et al. [76] compared 99mTc-nanocolloid with 99mTclabeled leukocytes and found similar sensitivities and specificties for infectious bone and joint disease. However, they had poor results for inflammatory bowel disease, infections of vascular grafts, and soft-tissue abscess. It is doubtful that an agent effective for bone and joint infections only will gain wide

acceptance. Current

Practice

A brief review of the radiologic litis is required before assessing

complex

on some

scintigraphic

In the past, gives excellent

other

process

that

requires

more

osteomyelitis. CT and is still used to

determine the cortical extent of bone infection. In addition, it is used to guide the biopsy in vertebral osteomyelitis or other procedures when fluoroscopy would be suboptimal. However, in most

situations,

MR imaging infection

CT has been replaced

has the best resolution

of any imaging

technique.

several studies that used MR imaging litis. When ity is 95%

by MR imaging.

of soft-tissue

Table

vs bone of

osteomye-

the results of Table 5 are added together, sensitiv(1 88/1 97) and specificity is 88% (1 03/1 1 7). How-

ever, any disease that replaces bone marrow and causes increased tissue water (e.g., healing fractures or tumors) may resemble osteomyelitis [78, 88]. In addition, artifacts caused by joint implants may degrade the images sufficiently to make diagnosis of infected joint arthroplasty impossible [88]. For osteomyelitis,

MR imaging

the three-phase

TABLE

gives

results

similar

to those

bone scan (Table 1) but is considerably

5: Results

of MR Imaging

Reference

Beltran et al. [77] Unger et al. [78] Tang et al. [79] Modic et al. [80] Yuh et al. [81] Beltran et al. [82] Zynamon et al. [83] Dalla Palma et al. [84] Wang et al. [85] Mason et al. [86] Hovi et al. [87]

myelitis in the bone marrow-containing skeleton can be difficult to diagnose. At present, the 99mTc bone marrow scan and I 1 1ln-labeled leukocyte scan appear to be the procedures of choice. The following procedures are experimental and may eventually lead to superior accuracy in the diagnosis of osteomyelitis.

99mTcHexamethylpropyleneamine

Oxime (HMPAO)-Labeled

Leukocytes Several techniques for labeling leukocytes with 99mTc have proposed, but the most generally accepted approach is the use of 99mTc-HMPAO. Preliminary results are encouraging (Table 6). When the results in Table 6 are added together, been

5 lists the results

to diagnose

Current scintigraphic diagnosis of osteomyelitis in various clinical situations can be summarized as follows: (1 ) If the suspected osteomyelitis is in a location that appears normal on the radiograph, the three-phase bone scan is highly sensitive and specific. In routine clinical practice, this situation should be the most common. (2) In neonates, the three-phase bone scan, with whole body imaging, is the first study. If these findings are normal, a 67Ga-citrate scan would be the second study. (3) Suspected acute or chronic complicating osteomyelitis in the non-marrow-containing skeleton can be evaluated by using the combined 99mTc bone scan-111lnlabeled leukocyte study. (4) Acute complicating osteomyelitis in the bone marrow-containing skeleton (e.g., hips and knees) I 1

evaluation.

CT was used to diagnose images of the bone cortex

expensive. At our institution, MR imaging is rarely used to diagnose osteomyelitis; however, its excellent resolution is often used to determine the extent of infection. This use of MR is similar to that proposed by Gold [89].

can be evaluated by using the mTc bone marrow scan and 1ln-Iabeled leukocyte study. (5) Chronic complicating osteo-

studies used for osteomyethe role of the scintigraphic

studies. Plain radiography should be the first study in every patient. Although the plain radiograph may be diagnostic, the characteristic bone changes require 1 0-1 4 days to develop [4]. It can also determine if the suspected osteomyelitis is superimposed

15

of

more

sensitivity is 87% (81/93) and specificity is 81 % (54/67). In general, leukocytes labeled with 99mTc-HMPAO and leukocytes labeled with ln would be expected to have similar false-positive and false-negative results because both procedures use leukocytes to carry the radionuclide to the site of infection.

Leukocytes

advantages.

labeled

with

99mTc-HMPAO

First, approximately

have

two

distinct

40 times as much radioac-

tivity is injected, which will allow the use of single-photon emission computed tomography (SPECT) and may produce higher sensitivity. Second, 99mTcHMPAO is easily produced from a kit and is always available. Indium-i 1 1 may not be

in Osteomyelitis Sensitivity

13/1 3 1 1/1 2 10/1 0 12/13 25/25 6/6 27/27 19/19 45/46 1 1/1 1 9/15

Specificity

8/9 22/23 4/4 13/14 17/19 5/7 12/14 1/2 13/16 2/3 6/6

TABLE 6: Results in Osteomyelitis

of “Tc-HMPAO-Labeled

Reference Vorne et al. [90] lvancevic et al. [30]

Vorne et al. [76] Roddie et al. [91 ] Ruther et al. [31 ] Verlooy et al. [92] Note.-HMPAO

Leukocyte

Sensitivity

Specificity

8/i 0 14/1 5 13/14

7/7 2/2 7/8

4/4 1 5/22

14/15

19/29 5/6

27/28

= hexamethylpropyleneamine

oxime.

Scans

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16

SCHAUWECKER

readily available in some hospitals. The chief advantage of using leukocytes labeled with ln is the ability to perform simultaneous 9Tc imaging of bone or bone marrow, which can better localize the infection to bone or soft tissue. Although leukocytes labeled with 1In or mTc-HMPAO provide good sensitivity and specificity, both require extensive separation and labeling. This procedure takes about 2 hr and requires considerable skill to ensure that the cells are not damaged. In order to obtain satisfactory results with labeled leukocytes, it is necessary to use undamaged, fully functional cells. New agents available as kits are being developed that will alleviate this difficulty.

AJR:158,

January

1992

of osteomyelitis can be readily diagnosed by scintigraphic techniques. However, a few clinical situations remain in which a definitive diagnosis is difficult to establish by using any of the known radiologic or scintigraphic approaches. It is hoped that in the future, clinicians will have even better methods available for diagnosing complicated cases of osteomyelitis.

ACKNOWLEDGMENTS

I thank Kathy Carison for organizational Natalie

for

secretarial

expertise

in the

assistance

completion

and Katie Mae

of this

manuscript.

REFERENCES

Labeled

Antibodies

Preliminary results from European studies [31 93, 94] that used either “Tcor 123l-Iabeled antigranulocyte antibodies appear favorable. The agent is available as a kit in Europe, and the possibility of phase Ill trials in the United States is being discussed. Experience with 1lnlabeled granulocytes suggests that this agent may have decreased sensitivity in chronic infections in which the granulocyte response is diminished [95]. On the other hand, Peters and Lavender [96] recommend pure granulocytes when studying chronic osteomyelitis so that none of the activity is wasted on nonneutrophilic cells. Antigranulocyte antibodies have been produced from mouse antibodies, and some adverse reactions have been reported. Further work is required to establish the role of antigranulocyte antibodies in the diagnosis of osteomyelitis. Recently, 1ln-labeled human polyclonal immunoglobulin G (lgG) against inflammation has been developed [97, 98]. Preliminary results are quite promising (Table 7). When the results of Table 7 are added together, sensitivity is 98% (39/40) and specificity is 86% (25/29). Because this agent is a human antibody, it should not produce the human antimouse antibody reaction that is seen occasionally with antigranulocyte antibody. The biodistribution of 1ln-labeled human polyclonal lgG is considerably different from that of labeled leukocytes. Thus, approximately four times the activity can be administered, which may result in higher sensitivity. Phase Ill trials should be completed in the United States before this article is published. The antibody is already available commercially in Europe. ,

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1 4. 15.

Conclusions

16.

In the past few years, new radiopharmaceuticals have been developed and old studies have been recombined to better localize bone and soft-tissue infection. Currently, most cases

1 7. 18. 1 9.

TABLE 7: Results of Labeled Human Polyclonal Immunoglobulin G Scans in Osteomyelitis 20. Rubin

Reference

Label

et al. [99]

111ln 1ln ‘Tc

Oyen et al. [100] Buscombe et al. [1011

Sensitivity

Specificity

12/12 23/23 4/5

12/12 5/9 8/8

21

22.

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