Molecular Imaging of Infection: The First 50 Years

Despite significant advances in the understanding of microorganisms and an increased availability of antimicrobial therapy, infection remains a major cause of morbidity and mortality. The diagnosis can be challenging and imaging studies often are used for confirmation and localization. For nearly 50 years, molecular imaging agents have played an important role in the diagnosis of infection. Gallium-67 citrate was perhaps the first molecular imaging agent used for diagnosing and localizing infection. Poor imaging characteristics, along with a lack of specificity, and the long (usually 48-72 hours) interval between administration and imaging motivated investigators to search for alternatives. Currently the role of ⁶⁷Ga is limited to differentiating acute tubular necrosis from interstitial nephritis and as an alternative to ¹⁸F-FDG for indications, such as sarcoid, spondylodiscitis, and fever of unknown origin, when the latter is not available. The development, in the mid-1970s, of techniques for radiolabeling leukocytes that subsequently migrate to foci of infection was a significant advance and labeled leukocyte imaging still has a preeminent role in molecular imaging of infection. There are significant disadvantages to in-vitro labeled leukocyte imaging. Efforts devoted to developing in-vivo leukocyte labeling methods, however, met with only limited success. Over the past 20 years ¹⁸F-FDG has established itself as the molecular imaging agent of choice for fever of unknown origin, vasculitis, sarcoid, and spondylodiscitis. As useful as these agents are, their uptake is based on the host response to infection, not infection itself. Previous attempts at developing infection specific agents, including radiolabeled antibiotics, antibiotics, and vitamins like biotin were limited by poor results and/or limited availability and so investigators continue to focus on developing infection specific molecular imaging agents. Initial results with radiolabeled nucleoside analogs, sugars, and amino acids, and a renewed interest in radiolabeled antibiotics for both diagnosis and monitoring treatment are exciting and hold great promise for the future.