indium-oxine and Infections

With a current annual mortality rate of around 35% worldwide, infection remains a significant concern, and the diagnosis and localization of infectious foci is an important health issue. As an established infection-imaging modality, nuclear medicine plays a vital health-care role in the diagnosis and subsequent effective treatment of this condition. Despite the development of several newer radiopharmaceuticals, (67)Ga and leukocyte imaging procedures have maintained their established place for infection. Several techniques in nuclear medicine significantly aid infection diagnosis, including imaging with (111)In-oxine-, (99m)Tc-hexamethylpropyleneamine oxime-, and (99m)Tc-stannous fluoride colloid-labeled leukocytes and with (67)Ga-citrate. Each radiopharmaceutical has specific advantages and disadvantages that make it suitable to diagnose different infectious processes (e.g., soft-tissue sepsis, inflammatory bowel disease, osteomyelitis, occult fever, fever of unknown origin, and infections commonly found in immunocompromised patients). After finishing this article, the reader should be able to identify the properties of an ideal radiopharmaceutical for infection imaging, list a range of available infection-imaging radiopharmaceuticals, compare the relative results of a range of radiopharmaceuticals used internationally to detect infection in the body, understand several common infectious processes that can be diagnosed using nuclear medicine techniques, and select an appropriate radiopharmaceutical to image a range of infectious processes.

Topics: Citrates; Fever of Unknown Origin; Gallium; Humans; Infections; Irritable Bowel Syndrome; Leukocytes; Nuclear Medicine; Organometallic Compounds; Osteomyelitis; Oxyquinoline; Practice Patterns, Physicians'; Predictive Value of Tests; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Sepsis; Technetium Compounds; Technetium Tc 99m Exametazime; Tin Fluorides; Tomography, Emission-Computed

Investigators have used various techniques and radionuclides such as 51Cr and 32P-diisofluorophosphate to label blood cells and to study cell survival. Early studies also used these radionuclides to label human leucocytes for cell survival by in-vitro counting. But external imaging could not be done with these agents. Starting with the use of the gamma-emitting radionuclide (111)In-oxine for in-vitro labelling of phagocytic leucocytes, external imaging became possible. This method was the basis of visualisation of cell distribution within the body. Because an abscess consists primarily of leucocytes, leucocytes labelled with (111)In localise within the abscess and are detectable by imaging. Nowadays other radiopharmaceuticals with other underlying uptake mechanisms are also used to detect inflammatory or infectious foci in patients. Nuclear medicine can be most useful in patients with fever of unknown origin, where a focus has to be defined, or in patients where a lesion is known by clinical symptoms or by a radiological imaging and the differentiation between infection and other pathologies has to be made.

Topics: Fever of Unknown Origin; Fluorine Radioisotopes; Gallium Radioisotopes; Humans; Indium Radioisotopes; Infections; Inflammation; Leukocytes; Nuclear Medicine; Organometallic Compounds; Oxyquinoline; Radioimmunodetection; Radiopharmaceuticals; Technetium Tc 99m Exametazime

Topics: Antibodies, Monoclonal; Humans; Indium Radioisotopes; Infections; Inflammatory Bowel Diseases; Iodine Radioisotopes; Leukocytes; Organometallic Compounds; Oxyquinoline; Predictive Value of Tests; Radionuclide Imaging; Technetium; Tissue Distribution

Radionuclide techniques for localizing inflammatory processes had relied heavily upon 67Ga-citrate until McAfee and Thakur described the technique for the radiolabeling of leukocytes with 111In-oxine. Since their initial description in 1976 there has been continued development of the radiopharmaceutical, as well as clinical efficacy. At present 111In-labeled leukocytes continue to be handled as an investigational new drug but this has not greatly limited its clinical availability. Indium-111 leukocytes are the agent of choice for evaluation of patients with fever of unknown origin, osteomyelitis, and prosthetic graft infections; and preliminary data shows great promise in the area of detecting reoccurrence of inflammatory bowel disease. This article attempts to review currently accepted uses of 111In leukocytes as well as potential areas of application.

Topics: Abscess; Blood Vessel Prosthesis; Colitis, Ulcerative; Crohn Disease; Cytomegalovirus Infections; Enterocolitis, Pseudomembranous; Fever of Unknown Origin; Gallium Radioisotopes; Humans; Indium; Infections; Inflammation; Leukocytes; Liver Abscess; Organometallic Compounds; Osteomyelitis; Oxyquinoline; Pancreatic Diseases; Radionuclide Imaging

We describe here a protocol for labelling autologous white blood cells with (111)In-oxine based on previously published consensus papers and guidelines. This protocol includes quality control and safety procedures and is in accordance with current European Union regulations and International Atomic Energy Agency recommendations.

Topics: Adult; Cell Separation; Chemotaxis, Leukocyte; Child, Preschool; Humans; Indium Radioisotopes; Infections; Inflammation; Isotope Labeling; Leukocytes; Organometallic Compounds; Oxyquinoline; Radiation Protection; Radionuclide Imaging; Radiopharmaceuticals; Tissue Distribution

Persistent fever in a 60-yr-old man with polycystic kidney and liver diseases and bilateral hip prostheses was presented in this study. Multiple diagnostic tests failed to localize a source of infection. Subsequently, a combination of a 111In-oxine labeled WBC and 99mTc-sulfur colloid scans (and computer subtraction) demonstrated abnormally increased WBC activity in the left lobe of the liver, thus, diagnosis of an infected cyst (or cysts) was made. The patient responded to the treatment with antibiotics. This article discusses the clinical features of polycystic disease of the liver and kidneys. Infection in cysts are discussed as well as radiographic and scintigraphic investigations that can be used to diagnose and localize infection in a cyst.

Topics: Cysts; Fever; Hip Prosthesis; Humans; Indium Radioisotopes; Infections; Leukocytes; Liver Diseases; Male; Middle Aged; Organometallic Compounds; Oxyquinoline; Polycystic Kidney, Autosomal Dominant; Radionuclide Imaging; Technetium Tc 99m Sulfur Colloid

Several chelates are available for leukocyte labeling. Studies indicate that cells labeled with any of the chelates have a sensitivity for infection of 90% to 95% when imaged at 24 hours postinjection. The sensitivity of 111In-labeled leukocytes at earlier imaging times is more controversial. There has been concern about the utility of labeled leukocytes in musculoskeletal infection. Recent leukocyte studies show a high sensitivity for infected prostheses, even though these infections are often walled off and do not cause systemic symptoms. However, leukocytes frequently miss osteomyelitis of the spine for reasons that are not known. Although some investigators do not recommend the use of 111In-labeled leukocytes in chronic infections, we have found a high sensitivity for infections that are 2 or more weeks old. Autopsy studies from the preantibiotic era indicate that bacterial infections with common organisms have high levels of neutrophil infiltration for months. Labeled lymphocytes from mixed-cell preparations also may play a role in detecting these inflammatory sites. Questions have been raised about the effect of antibiotic therapy on leukocyte sensitivity. Antibiotics do not appear to have a significant effect on scan sensitivity. By reducing the number of bacteria at an inflammatory site, antibiotics reduce the amount of chemotactic inhibitors. In addition, some antibiotics have been shown to directly stimulate leukocyte chemotaxis. Other factors that can theoretically reduce leukocyte function, including hemodialysis, hyperalimentation, hyperglycemia, and steroids, do not appear to reduce labeled leukocyte sensitivity for infection. The specificity of leukocyte uptake is reduced in the gastrointestinal tract and lungs. In these sites, uptake correlates with infection or the true cause of the patients' fever in only 10% to 50% of cases.

Topics: Chronic Disease; Digestive System; Humans; Indium Radioisotopes; Infections; Leukocytes; Lung; Organometallic Compounds; Osteomyelitis; Oxyquinoline; Radionuclide Imaging; Sensitivity and Specificity; Technetium Tc 99m Sulfur Colloid; Tropolone

Topics: Adult; Antibodies, Monoclonal; Antigen-Antibody Reactions; Female; Granulocytes; Humans; Indium Radioisotopes; Infections; Inflammatory Bowel Diseases; Male; Middle Aged; Organometallic Compounds; Organotechnetium Compounds; Oximes; Oxyquinoline; Radionuclide Imaging; Technetium Tc 99m Exametazime; Tissue Distribution

We report an analysis of the results obtained in our first 100 studies with indium-111-oxine labelled leukocyte scintigraphy, a diagnostic technique which has recently become available for clinical evaluation within Australia. We used this technique to assess patients with suspected sepsis or inflammation after other commonly used investigations had failed to confirm a diagnosis. Four patient subgroups were evaluated: fever of unknown origin; suspected abdominal or postoperative sepsis; suspected active inflammatory bowel disease; and suspected sepsis or inflammation of bones or joints. The course of all patients was followed for at least three months to establish the accuracy of the technique. The leukocyte labelling procedure took 90 min and imaging was carried out typically 3-6, 24 and occasionally 48 h after reinjection of the labelled autologous leukocytes. In one patient labelling of leukocytes was unsuccessful. In the remaining 99 studies the overall sensitivity of leukocyte scintigraphy was 88% (36 of 41 patients with a proved inflammatory or infective disease focus had positive scan findings); and the specificity was 95% (55 of 58 cases with no proved disease focus had normal scan findings). This series supports the use of this method as the imaging procedure of choice in nuclear medicine for the evaluation of suspected acute sepsis (symptoms less than four weeks' duration), of inflammatory bowel disease and of suspected infections involving appendicular bones which contain no active bone marrow. It is also a useful secondary scintigraphic procedure, after gallium-67-citrate scintigraphy, in patients with suspected infective disorders of more than four weeks' duration.

Topics: Abdomen; Adolescent; Adult; Aged; Aged, 80 and over; Bone Diseases; Female; Humans; Indium Radioisotopes; Infections; Inflammation; Inflammatory Bowel Diseases; Joint Diseases; Leukocytes; Male; Middle Aged; Organometallic Compounds; Oxyquinoline; Radionuclide Imaging

Although few reports address the use of three-phase bone scanning (TPBS) and 111In-labeled white blood cell (In-WBC) scintigraphy in hip arthroplasty utilizing a porous coated prosthesis, the literature suggests that scintigraphic patterns in the uncomplicated patient may differ from that seen in the cemented prosthesis. In an attempt to determine the scintigraphic natural history, 25 uncomplicated porous coated hip arthroplasties in 21 patients were prospectively studied with serial TPBS and In-WBC at approximately 7 days, and at 3, 6, 12, 18, and 24 mo postoperatively. This report deals with findings related to the prosthetic tip. Only one of 136 flow studies were abnormal and only two of 136 blood-pool images demonstrated focally increased activity. All 25 prostheses (120 of 143 scans) demonstrated increased uptake on the bone phase images. The area about the tip was divided into three segments; increased uptake at 24 mo was noted in the medial, distal, and lateral segments in 16%, 72%, and 56% of prostheses, respectively. Twenty of 25 prostheses (82 of 142 scans) showed uptake on In-WBC scintigraphy, being noted in 48% of prostheses at 24 mo. We conclude that scintigraphic patterns in the uncomplicated patient with a porous coated prosthesis appear to differ from patterns described in cemented prostheses.

Topics: Adult; Aged; Female; Hip Joint; Hip Prosthesis; Humans; Indium Radioisotopes; Infections; Leukocytes; Male; Middle Aged; Organometallic Compounds; Oxyquinoline; Prosthesis Failure; Radionuclide Imaging; Technetium Tc 99m Medronate

Indium-111-labeled leukocyte scans were performed on 39 patients with suspected musculoskeletal infections to assess the usefulness of this study in detecting bone and joint infections. Results of these scans, as well as results of technetium-99m bone scans, were correlated with the patients' final diagnoses. The indium scan had an overall sensitivity of 77%, a specificity of 69%, and an accuracy of 72%. In 10 patients with a duration of symptoms of six weeks or less, the sensitivity was 100% and the specificity was 75%. In 29 patients with symptoms of greater than six weeks, the sensitivity and specificity were lower at 50% and 71% respectively. Technetium-99m bone scans were performed on 23 patients; sensitivity for infection was 100% while specificity was 60%. Our results suggest that the indium-111 leukocyte scan is a useful adjunct in the diagnosis of acute musculoskeletal infections, but may be inconclusive in chronic infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bone Diseases; Child; Female; Humans; Hydroxyquinolines; Indium Radioisotopes; Infections; Leukocytes; Male; Middle Aged; Muscular Diseases; Organometallic Compounds; Oxyquinoline; Radionuclide Imaging

Indium-111 leukocyte scanning is a reliable means of locating acute infection in adults, but its use in the pediatric population has not been extensively documented. The results of scans on 30 children retrospectively reviewed are presented. Acute infections were detected in 15 of 16 patients (94% sensitivity) with one false negative scan. There were 8 truly negative and 6 falsely positive studies (57% specificity).

Topics: Adolescent; Child; Child, Preschool; Fever of Unknown Origin; Humans; Hydroxyquinolines; Indium; Infant; Infections; Leukocytes; Organometallic Compounds; Oxyquinoline; Radionuclide Imaging

There is considerable disagreement as to whether oxine or tropolone is the best labeling agent for indium leukocytes. We have previously looked at the sensitivity of oxine-labeled 111In leukocyte scans for occult infections and now present a similar group of patients imaged with tropolone-labeled 111In leukocytes. Thirty-four patients (38 studies) with possible occult infection were prospectively studied. Patients were imaged 1-4 hr after injection and again at 24 hr postinjection. The early tropolone images had a sensitivity of 53% while the delayed images at 24 hr had a sensitivity of 93%. Based on a previous study, oxine-labeled leukocyte scans have an early sensitivity of 33% and a delayed sensitivity (at 24 hr) of 95%. The differences in sensitivity between oxine and tropolone when imaged early and at 24 hr were not statistically significant. We conclude that there is no significant difference in the ability to detect infection between oxine- and tropolone-labeled leukocytes, both early at 1-4 hr, and on delayed imaging 24 hr after injection.

Topics: Abscess; Adult; Cycloheptanes; False Negative Reactions; Female; Humans; Hydroxyquinolines; Indium; Infections; Leukocytes; Male; Organometallic Compounds; Oxyquinoline; Prospective Studies; Radioisotopes; Radionuclide Imaging; Surgical Wound Infection; Time Factors; Tropolone

Topics: Animals; Blood Platelets; Blood Vessel Prosthesis; Dogs; Hydroxyquinolines; Indium; Infections; Organometallic Compounds; Oxyquinoline; Radioisotopes

Topics: Humans; Hydroxyquinolines; Indium; Infections; Leukocytes; Organometallic Compounds; Oxyquinoline; Radioisotopes; Radionuclide Imaging

A new nuclear scanning technique was found more specific for bone, joint, and soft tissue infections than any previously described scanning technique. The leukocyte scan, whereby a patient's own cells are labeled with a radioactive tagging agent (111In oxine), can distinguish an active infectious process from other pain-inducing conditions. Ninety-seven 111In labeled autologous leukocyte scans were performed in 88 patients. The findings in 17 of 40 patients scanned for possible acute osteomyelitis, six of nine for suspected septic arthritis, and six for possible soft tissue infections, were positive. Subsequent clinical courses verified the infectious nature of these processes in all patients. Patients who had chronic osteomyelitis (14), bony metastases (four patients), heterotopic ossification (three), and degenerative arthritis (two) demonstrated negative findings. Of the seven patients scanned for acute long-bone fractures, one demonstrated positive findings. Nine scans demonstrated positive findings without determined causes. The leukocyte scan is a useful addition to the diagnostic tools of the orthopedic surgeon.

Topics: Adult; Aged; Bone Diseases; Bone Neoplasms; Female; Fractures, Bone; Humans; Indium; Infections; Isotope Labeling; Joint Diseases; Leukocytes; Male; Middle Aged; Neoplasm Metastasis; Organometallic Compounds; Ossification, Heterotopic; Oxyquinoline; Radioisotopes; Radionuclide Imaging