Nuclear medicine imaging of bone infections.

Osteomyelitis is a broad group of infectious diseases that involve the bone and/or bone marrow. It can arise haematogenously, via extension from a contiguous infection, or by direct inoculation during surgery or trauma. The diagnosis is not always obvious and imaging tests are frequently performed as part of the diagnostic work-up. Commonly performed radionuclide tests include technetium-99m ((99m)Tc)-diphosphonate bone scintigraphy (bone), and gallium-67 ((67)Ga) and in vitro labelled leukocyte (white blood cell; WBC) imaging. Although they are useful, each of these tests has limitations. Bone scintigraphy is sensitive but not specific, especially when underlying osseous abnormalities are present. (67)Ga accumulates in tumour, trauma, and in aseptic inflammation; furthermore, there is typically an interval of 1-3 days between radiopharmaceutical injection of and imaging. Currently, this agent is used primarily for spinal infections. Except for the spine, WBC imaging is the nuclear medicine test of choice for diagnosing complicating osteomyelitis. The in vitro leukocyte labelling process requires skilled personnel, is laborious, and is not always available. Complementary marrow imaging is usually required to maximise accuracy. Not surprisingly, alternative radiopharmaceuticals are continuously being investigated. Radiolabelled anti-granulocyte antibodies and antibody fragments, investigated as in vivo leukocyte labelling agents, have their own limitations and are not widely available. (111)In-biotin is useful for diagnosing spinal infections. Radiolabelled synthetic fragments of ubiquicidin, a naturally occurring human antimicrobial peptide that targets bacteria, have shown promise as infection specific radiopharmaceuticals. 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) with or without computed tomography (CT) is very useful in musculoskeletal infection. Sensitivities of more than 95% and specificities ranging from 75-99% have been reported in acute and subacute bone and soft-tissue infection. FDG is the radionuclide test of choice for spinal infection. It is sensitive, has a high negative predictive value, and can differentiate degenerative from infectious vertebral body end-plate abnormalities. Data on the accuracy of FDG for diagnosing diabetic pedal osteomyelitis and prosthetic joint infection are inconclusive and its role for these indications remains to be determined. Other PET radiopharmaceuticals that are under investigation as infection imaging agents include gallium-68 citrate ((68)Ga) and iodine-124 fialuridine ((124)I -FIAU).

Imaging of infection and inflammation with 99mTc-Fanolesomab.

(99m)Tc-fanolesomab, a murine M class antigranulocyte antibody, is injected directly into patients, avoiding in vitro leukocyte labeling. Normal distribution includes reticuloendothelial system, genitourinary tract, and blood pool. Small bowel activity appears within 4 h, colonic activity by 24 h. Accumulation in infection is via two mechanisms: binding to circulating neutrophils that migrate to the infection and binding to neutrophils and neutrophil debris containing CD-15 receptors already sequestered in the infection. (99m)Tc-fanolesomab is valuable in atypical appendicitis. Its sensitivity, specificity, and accuracy, in 200 patients were 91%, 86%, and 87%, respectively. This agent is comparable to (111)In- labeled leukocytes for diagnosing osteomyelitis in the appendicular skeleton in general and in diabetic patients with pedal ulcers. Preliminary experience suggests (99m)Tc-fanolesomab might replace in vitro labeled leukocytes for other indications as well. Initial clinical investigations found the agent was safe. A transient decrease in circulating leukocytes within 20 min after injection occurred, but with no associated clinical complaints. Recovery averaged about 20 min. One study found no statistically significant HAMA titer elevation and no adverse reactions following injection. In another investigation 5 out of 30 subjects who received two separate antibody injections, exhibited HAMA induction with no serious or severe adverse events. Forty-nine adverse events, including 4 severe ones, were reported among 523 subjects in clinical trials. In 2004, (99m)Tc-falosomab was approved in the United States for use in patients with equivocal presentation of appendicitis. However, following postmarketing reports of serious adverse events, including two fatalities, the agent was withdrawn in late 2005, and its future is uncertain.