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Scintigraphic evaluation of chronic osteomyelitis with technetium-99m labeled polyclonal immunoglobulin
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The diagnostic accuracy of scintigraphy performed after injection of indium-111-labeled nonspecific human immunoglobulin G (IgG) was studied in 113 patients with 120 foci of suspected infection in bone (52 chronic and eight acute infections), joints (15 localizations), joint prostheses (37 prostheses), and soft tissue of the locomotor system (eight localizations). All patients also underwent standard three-phase scintigraphy after injection of technetium-99m-labeled methylene diphosphonate. A scan obtained with In-111-labeled IgG was considered positive if focal increasing accumulation was noted over time. In 51 patients (45.1%), the results of scintigraphy were verified with intraoperative cultures, and in 21 patients (18.6%), with needle aspiration. The prevalence of infection was 59%; overall sensitivity, 97%; and specificity, 85%. Use of In-111-labeled IgG enabled correct identification of the presence, site, and extent of infection in 69 of 71 proved foci of infection; 41 of 48 negative studies were correct. Only two infections proved with culture were missed; in both patients, the cultures revealed growth of Staphylococcus aureus in low counts.
Gallium-67 and 3-phase bone scan (3P) studies, though very sensitive, are not very specific in evaluating suspected osteomyelitis (OM) which is superimposed upon other diseases that cause increased bone turnover (IBT). The authors compared In-111 acetylacetone labeled granulocytes (In-111) GRAN) with 3P in 57 such patients; 29 of these patients had Ga-67 studies as well. In-111 GRAN had a sensitivity of 100% in acute OM, 62% in chronic OM, and a specificity of 96%. Gallium-67 ruled out OM when the study was normal; it diagnosed OM when the relative uptake of Ga-67 exceeded the uptake of Tc-99m MDP, or when the skeletal distribution of Ga-67 was different from that of the TC-99m MDP. Unfortunately, these criteria were met in only 28% of the subjects. The simple approach of increased Ga-67 activity meant OM gave a sensitivity of 100%, but an unacceptable specificity of 38%. Chronic cellulitis or long-standing decubiti were seldom detected by IN-111 GRAN. Clinically obvious soft tissue infections or cellulitis were seen with In-111 GRAN 27% of the time, and 17% of the time with Ga-67. The authors conclude that when added to 3P, In-111 GRAN provided more useful information than did Ga-67. A combination of all 3 studies did not significantly increase the diagnostic yield. Performing In-111 GRAN without 3P in patients with IBT is not recommended since the 3P provides anatomic information that aids in the differentiation of OM from soft tissue infections.
The accuracy of technetium-99m human immunoglobulin (HIG) for the detection of chronic osteomyelitis (OM) was compared with white blood cell scintigraphy using99mTc-labelled monoclonal mouse antibodies (MAB). Seventeen patients suspected of having OM in 20 lesions went through three-phase skeletal scintigraphy, HIG scintigraphy and MAB scintigraphy. The final diagnosis was established by open surgery, histology and bacteriology. Chronic OM was proved in 14/20 lesions. Six of these 14 infections were located in peripheral areas without active bone marrow and 8/14 in central areas with active bone marrow. In peripheral OM, 5/6 with HIG and 6/6 with MAB were true positives. In the central skeleton all 8/8 infections appeared as cold lesions in the MAB study, which were defined as being false negative due to their non-specificity. Using HIG, 5/8 central infections were determined to be truly positive by showing photon-rich lesions. These 5 lesions were located in the hip region and in the pelvis, whereas 3 lesions of the spine were missed. There were no false-positive results in either studies. In conclusion, MAB was superior to HIG in peripheral OM concerning sensitivity, anatomical landmarks and differentiation of soft tissue versus bone infection. In central OM MAB detected all lesions accurately, but no differential diagnosis was possible due to the non-specificity of photon-low areas. In this respect HIG seems to be more specific due to the increased accumulation even in central infection sites.
The detection of focal sites of inflammation is an integral part of the clinical evaluation of the febrile patient. When anatomically distinct abscesses are present, lesion detection can be accomplished by standard radiographic techniques, particularly in patients with normal anatomy. At the phlegmon stage, however, and in patients who have undergone surgery, these techniques are considerably less effective. While radionculide methods, such as Gallium-67 (87Ga)-citrate and Indium-111 (111In)-labeled WBCs have been relatively successful for the detection of early inflammation, neither approach is ideal. In the course of studies addressing the use of specific organism-directed antibodies for imaging experimental infections in animals, we observed that non-specific polyclonal immunoglobulin G (IgG) localized as well as specific antibodies. Preliminary experiments suggested that the Fc portion of IgG is necessary for effective inflammation localization. Since polyclonal IgG in gram quantities has been safely used for therapy in patients with immune deficiency states, we decided to test whether milligram quantities of radiolabeled IgG could image focal sites of inflammation in humans. Thus far, we have studied a series of 84 patients with suspected lesions in the abdomen, pelvis, vascular grafts, lungs, or bones/joints. In 48 of 52 patients with focal lesions detected by surgery, computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound (US), the IgG scan correctly localized the site, while 31 patients without focal inflammation had no abnormal focal localization of the radiopharmaceutical. Four patients had false negative scans and one patient had a false positive scan. For this small series, the overall sensitivity and specificity were 92% and 95%, respectively. In this report, we review our experience with this exciting new agent.
The role of gallium imaging in infection has changed considerably during the past several years. Once the mainstay of radinuclide, imaging of infection, it has been supplanted to a very great extent by labeled leukocyte imaging. Despite the success of the labeled white-cell technique, gallium still plays an important role in the radionuclide evaluation of infection. It is not possible, for a variety of reasons, to perform white-cell imaging on all patients, and gallium imaging is certainly an acceptable substitute. In certain circumstances, rather than merely being a substitute, gallium is an important complement to leukocyte imaging. This is best illustrated by the patient with a fever of unknown origin (FUO). Although a negative leukocyte study effectively excludes an acute infection, it fails to identify the source of the patient's fever, a not uncommon situation in view of the fact that only approximately 25% of all FUOs are caused by infection. A complementary gallium study under these circumstances may identify either a chronic infectious process or even a neoplasm, conditions for which white-cell imaging is relatively insensitive. Although leukocyte imaging is probably superior to gallium for most infections of the musculoskeletal system, this technique is of limited value in patients with suspected vertebral osteomyelitis. There are data that suggest that sequential bone gallium imaging may be a better way to diagnose this entity. Finally, in immunocompromised patients, gallium imaging is clearly the procedure of choice for detecting the opportunistic respiratory infections and lymph node abnormalities that are so prevalent in this population.
Osteomyelitis is a serious health problem that results in multiple limb amputations annually. This article reviews the current scintigraphic procedures used in the diagnosis of osteomyelitis and discusses some of the newer radiopharmaceuticals now being developed. The goal is to understand the strengths and weaknesses of each method so that the procedure most effective for specific clinical settings can be selected. In general, the three-phase 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 111In-labeled leukocyte-99mTc bone scan is the procedure of choice in the non-marrow-containing skeleton and the 111In-labeled leukocyte and 99mTc bone marrow scans are the procedures of choice in the marrow-containing skeleton.
The accuracy of technetium-99m human immunoglobulin (HIG) for the detection of chronic osteomyelitis (OM) was compared with white blood cell scintigraphy using 99mTc-labelled monoclonal mouse antibodies (MAB). Seventeen patients suspected of having OM in 20 lesions went through three-phase skeletal scintigraphy, HIG scintigraphy and MAB scintigraphy. The final diagnosis was established by open surgery, histology and bacteriology. Chronic OM was proved in 14/20 lesions. Six of these 14 infections were located in peripheral areas without active bone marrow and 8/14 in central areas with active bone marrow. In peripheral OM, 5/6 with HIG and 6/6 with MAB were true positives. In the central skeleton all 8/8 infections appeared as cold lesions in the MAB study, which were defined as being false negative due to their non-specificity. Using HIG, 5/8 central infections were determined to be truly positive by showing photon-rich lesions. These 5 lesions were located in the hip region and in the pelvis, whereas 3 lesions of the spine were missed. There were no false-positive results in either studies. In conclusion, MAB was superior to HIG in peripheral OM concerning sensitivity, anatomical landmarks and differentiation of soft tissue versus bone infection. In central OM MAB detected all lesions accurately, but no differential diagnosis was possible due to the non-specificity of photon-low areas. In this respect HIG seems to be more specific due to the increased accumulation even in central infection sites.
Über die Biodistribution von 99mTc- markiertem humanem Immunglobulin, einem neuen Pharmakon zur Lokalisation entzündlicher Erkrankungen, liegen bislang am Menschen nur unzureichende Daten vor. Bei einem freiwilligen Probanden, bei dem eine physiologische Biokinetik vorausgesetzt werden konnte, wurden diese Daten erhoben und die Organdosen gemäß dem MIRD-Konzept berechnet. Planare Szintigramme in p.a.- und a.p.-Projektion nach 1, 2, 4 und 24 h p.i. ließen eine prolongierte Aktivitätsretention im Blut und einen Nieren-, Blasen- und Leber-Uptake erkennen. Ein signifikanter Darmoder Knochenmarksuptake war während der gesamten Untersuchungsdauer nicht zu registrieren. 27,4% der applizierten Aktivität wurden renal eliminiert. Die Organdosen (in μGy/ MBq) wurden wie folgt abgeschätzt: Ganzkörper 2,7; Leber 7,3; Milz 12,0; Nieren 15,3; Lungen 3,2; Knochenmark 9,6; Gonaden 17,0. Aus diesen Ergebnissen wurde ein effektives Dosisäquivalent von 7,9 × 10⁻³ mSv/MBq errechnet. Das Ergebnis der Krebsrisikoabschätzung von 5 × 10⁻⁵ beim Einsatz von 370 MBq 99mTc-HIG erwies sich im Vergleich zu anderen szintigraphischen Techniken zur Entzündungslokalisation als recht niedrig.
* Research supported by the Johannes und Frieda Marohn-Stiftung at the University of Erlangen-Nürnberg.
Technetium (99mTc) labelled, polyclonal human immunoglobulin (HIG) is a new agent that detects focal infection and inflammation. This new agent was compared in 40 patients with the accepted standard, namely 111In-oxine-labelled leucocytes. This comparison resulted in a sensitivity of 94% and a specificity of 96% for 99mTc-HIG when 111In-oxine leucocytes were defined as giving the true result. The new agent was shown to localize both sepsis and active inflammatory bowel disease (IBD). There was 100% concordance in the 16 patients with IBD who were imaged with both 99mTc-HIG and 111In-oxine leucocytes. Discordant results were obtained in one case of suspected osteomyelitis, which was false-positive on the 99mTc-HIG scan, and one case of pyrexia of unknown origin when the 99mTc-HIG was false-negative and the 111In-oxine leucocyte scan demonstrated accumulation of tracer in the caecum at 24 h post-injection. Normal distribution for 99mTc-HIG demonstrated activity in the kidneys and bladder and that 50% of the tracer is cleared through the kidneys during the first 24 h post-injection. There were no major or minor side-effects.