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 (^99mTc)-diphosphonate bone scintigraphy (bone), and gallium-67 (⁶⁷Ga) 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. ⁶⁷Ga 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. ¹¹¹In-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-[¹⁸F]-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 (⁶⁸Ga) and iodine-124 fialuridine (¹²⁴I -FIAU).