technetium-tc-99m-exametazime and Fever-of-Unknown-Origin

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

The spectrum of infectious diseases has changed over the last few years, hence the requirements for radionuclide imaging for the detection of infection are becoming more demanding so that, although gallium-67 and labelled leucocytes remain useful agents, there is currently great interest in the development of new agents especially able to target chronic, non-pyogenic inflammation. Agents can be classified according to the site at which the radiolabel is targeted: pre-endothelial (for example, labelled leucocytes), endothelial (for example, labelled anti-endothelial monoclonal antibodies) or post-endothelial (for example, fluorine-18-fluorodeoxyglucose (FDG)). 67Ga and labelled polyclonal human immunoglobulin (HIG) localize at inflammation initially as a result of increased endothelial permeability, followed by retention of the label through binding to local extravascular receptors. Labelled leucocytes are avidly taken up by acute pyogenic inflammatory foci but perform less well in chronic inflammation. Other indications for labelled leucocytes include bone infection and undiagnosed fever. Nevertheless, since many causes of the latter do not stimulate a neutrophilic infiltrate, a non-specific agent, such as 67Ga, FDG or HIG, may be preferable, especially in patients with no immediate significant medical history. Since endothelial E-selectin expression is closely correlated to lymphocyte migration, labelled anti-E-selectin monoclonal antibody may also have a potential role for imaging chronic inflammation.

Topics: Biomarkers; Fever of Unknown Origin; Fluorodeoxyglucose F18; Gallium Radioisotopes; Humans; Infections; Inflammation; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Exametazime

The authors describe the variability of Tc-99m exametazime-labeled leukocyte distribution as a function of the relative frequency of white cell types in the labeled blood.. A 76-year-old man who was hospitalized with fever and possible postoperative osteomyelitis underwent scintigraphic imaging with Tc-99m exametazime-labeled leukocytes.. The white cell scan excluded any discrete focus of infection and revealed diffuse involvement of the lymph nodes and skin. The pathologic diagnosis was angioimmunoblastic T-cell lymphoma. The atypical infiltrates seen on the white cell scan can be explained by the severe eosinophilic blood count on the day of leukocyte labeling (total leukocyte count: 8,100 cells/microl with 63% neutrophils, 8.9% lymphocytes, and 22.2% eosinophils).. In the labeling of the leukocyte moiety, a higher presence of any leukocyte subpopulation will modify the biodistribution and thus the image interpretation.

Topics: Aged; Diagnosis, Differential; Eosinophilia; Fever of Unknown Origin; Humans; Knee Prosthesis; Leukocytes; Lymphoma, T-Cell; Male; Prosthesis-Related Infections; Radionuclide Imaging; Radiopharmaceuticals; Technetium Tc 99m Exametazime; Whole-Body Counting

The results of the survey carried out in our country during the present year on the nuclear medicine studies in infectious and inflammatory studies during 1999 are presented. They survey was sent to 89 centers with a nuclear medicine service, 45 of which were publicly owned and 44 of which were privately owned. A total of 32 centers (36%) replied to the survey. 51.1% (23 out of 45) of the public hospitals responded but only a 20.5% (9 out of 44) of the private ones did.A total of 70.92% (4,344) out of the 6,125 explorations were carried out to discard and infectious process and 29.07% (1,781) to discard inflammation. The most frequent indication was to discard infections resulting from bone prostheses (2,099 explorations accounting for 48.31% of the total infectious process), followed by bone infection or osteomyelitis (965 explorations, 22.21% of the total). Within the osteomyelitis cases, acute processes motivated the most frequent requests (60.31% of all osteomyelitis cases). Assessment of the scope and localization of the intestinal inflammatory disease was the most frequent request in the inflammation group. Concerning the radiopharmaceuticals used, 99mTc HMAPO or 111I marked-leukocytes were ranked first, these accounting for 47% of the cases. Gallium, used in 44% of all cases, was the second most frequently used, even though it continues to be the more commonly used radiopharmaceuticals for infectious processes.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Drug Utilization; Fever of Unknown Origin; Gallium Radioisotopes; Health Care Surveys; Hospitals, Public; Humans; Infections; Inflammation; Intestinal Diseases; Iodine Radioisotopes; Leukocytes; Nuclear Medicine; Osteomyelitis; Prosthesis-Related Infections; Radionuclide Imaging; Radiopharmaceuticals; Spain; Technetium Tc 99m Exametazime

Fever of unknown origin is defined as a temperature above 39.0 degrees C together with a white blood cell count > or = 15,000 mm-3, the duration of fever exceeding 2 weeks and a correct diagnosis not being obtained in the first week of hospitalization. In neonates and infants with fever of unknown origin, the localization of the infectious focus is often difficult and unsatisfactory. In this retrospective study, the clinical value of 99Tcm-labelled antigranulocyte antibodies for this group of patients was investigated. Thirty-two immunoscintigrams were performed using 185-259 MBq 99Tcm-labelled antigranulocyte antibodies (BW 250/183) in 30 neonates and infants (21 boys, 9 girls, mean age 29.4 +/- 2 months), who had fever of unknown origin. Immunoscintigraphy was carried out as whole-body images (n = 7) or single planar images (n = 25) 4 h and 24 h post-injection. In children with known cardiac failure, single photon emission tomography of the thorax was performed to diagnose endocarditis (n = 2). For verification, the results of the immunoscintigrams were compared with radiology (conventional radiography = 14, MRI = 5, CT = 3), biopsy (n = 2), blood culture (n = 10) and clinical follow-up after specific therapy. In 11 of 30 children (36%), the diagnosis of an infective focus was possible with immunoscintigraphy. The sensitivity and specificity of diagnosing infective foci was 72% and 95% respectively (n = 11; colitis = 2, infection of the central permanent catheter tip = 2, middle ear infection = 1, spondylitis/discitis = 3, osteomyelitis = 2, umbilical infection = 1). In vertebral body infections, all lesions were photopenic. In 18 children (60%), no infective focus was found on immunoscintigraphy. In this group of children, the main reason (n = 5) for fever of unknown origin was chronic juvenile rheumatoid arthritis. No uptake was seen in two infants with cardiac failure and suspected endocarditis on SPET. In 3 of the 18 patients (17%), localization of an infective focus was not possible with immunoscintigraphy or on other examinations. In these patients, the fever disappeared spontaneously after a few days of antibiotic therapy. In conclusion, we have shown that 99Tcm-anti-NCA-95 scanning is a safe method with a high sensitivity and specificity for detecting infectious foci in neonates and infants with fever of unknown origin. Furthermore, this method is easy to perform, since no withdrawal of blood is necessary.

Topics: Antibodies, Monoclonal; Child, Preschool; Female; Fever of Unknown Origin; Granulocytes; Humans; Indium Radioisotopes; Infant; Infant, Newborn; Infections; Male; Radioimmunodetection; Retrospective Studies; Sensitivity and Specificity; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

The authors present a case in which Tc-99m HMPAO labeled autologous leukocytes were used to demonstrate a brain abscess in a patient undergoing evaluation for fever of unknown origin. The abscess was demonstrated on both 1-hour and 24-hour images. The positive 1-hour image led to CT and MRI studies, which are included for correlation. In addition to its previously identified role as a secondary diagnostic test in the differentiation of tumor and abscess, the authors propose that Tc-99m HMPAO is useful as a primary diagnostic tool in the identification of brain abscess. Furthermore, the authors suggest that Tc-99m HMPAO is preferable to In-111 labeled leukocytes because of its better resolution and earlier imaging characteristics.

Topics: Aged; Brain Abscess; Fever of Unknown Origin; Frontal Lobe; Humans; Image Enhancement; Indium Radioisotopes; Leukocytes; Magnetic Resonance Imaging; Male; Radionuclide Imaging; Radiopharmaceuticals; Streptococcal Infections; Streptococcus; Technetium Tc 99m Exametazime; Time Factors; Tomography, X-Ray Computed; Transplantation, Autologous; Whole-Body Counting

Technetium-99m hexamethylpropylene amine oxime (HMPAO)-labeled leukocytes are well established for the investigation of inflammatory disease. Their kinetics and normal distribution are similar to those of indium-111-labeled leukocytes except for nonspecific activity in urine, kidneys, gall bladder, and bowel, which results from the elution of secondary 99mTc-labeled HMPAO complexes. The principal clinical indications for [99mTc]HMPAO-leukocytes include inflammatory bowel disease (IBD), osteomyelitis, soft tissue sepsis, and, to a lesser extent, occult fever. The superior resolution and count density of 99mTc places [99mTc]HMPAO-leukocytes at an advantage over 111In-leukocytes in IBD, especially for the identification of small bowel involvement in patients with Crohn's disease. However, quantification of disease activity is more difficult than with 111In. Technetium-99m HMPAO-leukocytes are indicated for most forms of acute soft tissue and abdominal sepsis, although when compared with 111In, it may be more difficult to demonstrate communication between an abdominal abscess and bowel lumen. Chronic osteomyelitis, including infected joint prostheses, are better approached with 111In-labeled leukocytes. Occult fever and fever of unknown origin (FUO) are more controversial. There is still a place for gallium-67 in FUO, of which there is a wide spectrum of causes. Occult fever implies a pyogenic cause for an undiagnosed fever and should probably be imaged with 111In-leukocytes. With the advances being made in other imaging modalities and in interventional radiology, there is a clear need for radionuclide agents that can be used for whole-body screening in patients with undiagnosed fever. Such agents may include fluorine-18-fluorodeoxy-glucose and radiolabeled monoclonal antibodies to endothelial adhesion molecules activated at the foci of inflammation.

Topics: Bone and Bones; Digestive System; Fever of Unknown Origin; Humans; Infections; Inflammatory Bowel Diseases; Leukocytes; Organotechnetium Compounds; Osteomyelitis; Oximes; Radionuclide Imaging; Technetium Tc 99m Exametazime; Thoracic Diseases

A patient with a fever of unknown origin was evaluated by abdominal SPECT using Tc-99m HMPAO labeled granulocytes and a triple detector camera. Although no abscesses were located, nonpustular psoriatic skin lesions were demonstrated incidentally on the reprojectional images. Psoriatic scales contain a chemotactic factor for leukocytes, and this is a likely explanation for the increased uptake of the radiotracer by psoriatic lesions.

Topics: Fever of Unknown Origin; Granulocytes; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Psoriasis; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Four patients with the acquired immunodeficiency syndrome (AIDS) and fever were investigated using donor leucocyte scans. The lung/liver and lung/spleen uptake ratios in these patients were compared with the uptake ratios in donor leucocyte scans in seven neutropenic (non-AIDS) patients and five patients who had autologous leucocyte scans performed over the same time period. For all scans indium-111-oxime-labelled leucocytes were used, except for one AIDS patient in whom technetium-99m hexamethyl-propylene amine oxide (HMPAD)-labelled donor leucocytes were used. There were no adverse reactions to the donor cell infusions. Two patients had repeat studies 8 weeks apart (from different donors) without ill effect. There were no differences in the 111In uptake ratios between the three groups. There were three positive studies in the patients with AIDS, and these elucidated the cause of the pyrexia in all three. The negative case is more difficult to confirm, but the clinical course and the absence of focal disease on post-mortem have been taken to support the scan findings. There was no difference in the acceptability of the technique or the distribution of the labelled leucocytes between the AIDS and non-AIDS patients. Donor leucocyte imaging of patients with AIDS is probably more effective and considerably less hazardous for technical staff than autologous leucocyte methods. This study demonstrates that the technique can be applied successfully to patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Bacterial Infections; Blood Donors; Fever of Unknown Origin; Humans; Indium Radioisotopes; Isotope Labeling; Leukocytes; Middle Aged; Opportunistic Infections; Organometallic Compounds; Organotechnetium Compounds; Oximes; Oxyquinoline; Radionuclide Imaging; Technetium Tc 99m Exametazime

Topics: Abdomen; Abscess; Adolescent; Adult; Aged; Aged, 80 and over; Arteriovenous Shunt, Surgical; Child; Evaluation Studies as Topic; False Negative Reactions; False Positive Reactions; Female; Fever of Unknown Origin; Humans; Infections; Male; Middle Aged; Organotechnetium Compounds; Osteitis; Oximes; Radionuclide Imaging; Surgical Wound Infection; Technetium Tc 99m Exametazime

Topics: Adolescent; Crohn Disease; Fever of Unknown Origin; Humans; Leukocytes; Male; Organometallic Compounds; Oximes; Radionuclide Imaging; Technetium Tc 99m Exametazime

Leukocytes labeled with technetium-99m hexamethylpropyleneamine oxime (HMPAO) were used in 100 patients: 32 with suspected inflammatory bowel disease, 17 with fever of unknown origin, 21 with suspected abdominal sepsis, 20 with suspected bone sepsis, seven with bronchiectasis, and three with recent myocardial infarction. The distribution of activity in patients subsequently shown not to have inflammatory bowel disease was similar to that previously described for indium-111-labeled leukocytes. However, in this study, activity was also seen in the kidneys and bladder and occasionally the gallbladder on both early (1-3 hours) and late (24 hours) views, and in the colon in late views. Migration of Tc-99m-labeled granulocytes was seen in inflammatory disease as early as 30 minutes after injection, while normal bowel activity was not seen before 4 hours. The sensitivity of Tc99m-labeled leukocytes in the detection of inflammation was 100%, the specificity was 95%.

Topics: Colitis; Crohn Disease; Fever of Unknown Origin; Humans; Inflammation; Leukocytes; Organometallic Compounds; Osteitis; Oximes; Radionuclide Imaging; Technetium; Technetium Tc 99m Exametazime