Labeled leukocyte imaging: current status and future directions

The ability to radiolabel inflammatory cells that migrate to foci of infection was a significant milestone in the evolution of infection imaging. More than 20 years after being approved for clinical use in the United States, labeled leukocyte imaging using cells labeled with [(99m)Tc]exametazime or [(111)In]oxine remains the radionuclide procedure of choice for diagnosing most infections in the immunocompetent population. In the central nervous system, labeled leukocyte imaging is useful for differentiating infection from tumor; in the postoperative setting, this test facilitates the differentiation of infection from normal postoperative changes. Labeled leukocyte imaging accurately diagnoses mycotic aneurysms and infected prosthetic vascular grafts. In patients with fever of unknown origin, a negative study excludes, with a high degree of certainty, infection as the source of fever. Labeled leukocyte imaging accurately diagnoses pedal osteomyelitis and is useful for distinguishing infection from the neuropathic joint in this population. Together with bone marrow imaging, the labeled leukocyte study is the imaging procedure of choice for diagnosing prosthetic joint infection. There are limitations to the test. Most of the leukocytes labeled are neutrophils, and the procedure is most useful for detecting neutrophil-mediated inflammatory processes, i.e., bacterial infections. It is less useful for illnesses in which the predominant cellular response is other than neutrophilic, such as most opportunistic infections and spinal osteomyelitis. The in vitro labeling procedure is time consuming and is not routinely available. Results of in vivo leukocyte labeling methods have been variable; none are available in the United States. Labeled leukocyte imaging suffers from inherently poor quality images. Single photon emission compute tomography/computed tomography improves lesion localization, and will undoubtedly improve the accuracy of the test. Efforts to develop methods of labeling white cells with positron emitting compounds are underway and, if successful, should further strengthen the role of nuclear medicine in infection imaging.