Multiagent imaging of inflammation and infection w

Authors: Christopher J Palestro Andor W J M Glaudemans Rudi A J O Dierckx

Publish Date: 2013/11/23

Volume: 1, Issue: 6, Pages: 385-396

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Abstract

Molecular imaging with single photon and positronemitting tracers plays an important role in the evaluation of inflammation and infection Although supplanted by labeled leukocyte imaging for most indications gallium67 remains useful for opportunistic infections pulmonary inflammation and interstitial nephritis and when 18FFDG is not available spinal infection and fever of unknown origin In vitro labeled leukocyte imaging is the radionuclide procedure of choice for most infections in immunocompetent patients When performed for musculoskeletal infection complementary bone marrow imaging usually is necessary Recent data suggest that dual time point imaging might be an alternative to marrow imaging Several methods of labeling leukocytes in vivo with agents including antigranulocyte antibodies and antibody fragments peptides and cytokines have been investigated with variable results These agents are not widely available and none of them are available in the USA Radiolabeled antibiotics have been investigated as “infectionspecific” tracers but the results to date have been disappointing Conversely radiolabeled antimicrobial peptides do hold promise as infectionspecific tracers The use of positronemitting tracers for diagnosing inflammation and infection has generated considerable interest 18FFDG is useful in fever of unknown origin spinal osteomyelitis vasculitis and sarcoidosis Other positronemitting tracers that have been investigated include 18FFDGlabeled leukocytes copper64labeled leukocytes gallium68 citrate and iodine124 FIAU Although radiolabeled tracers are used primarily for diagnosis they also offer objective biomarkers for assessing response to therapeutic interventions in inflammatory diseases They could also potentially be used to target cells and molecules with specific receptor expression for histological characterization select patients for receptortargeted therapy and predict response to treatmentDespite significant advances in our understanding of microorganisms and the pathogenesis of inflammation and infection infection remains a major cause of patient morbidity and mortality Although signs and symptoms such as fever pain general malaise and abnormal laboratory results may suggest the presence of infection the diagnosis can be elusive and imaging tests often are used for confirmation and localization There are two principal categories of imaging tests anatomical or morphological and molecular Anatomical imaging tests such as radiographs ultrasound and computed tomography CT reveal structural alterations in tissues and organs caused by microbial invasion and the inflammatory response of the host Prototypical molecular imaging tests use agents such as gallium68 citrate labeled leukocytes and fluorine18 fluorodeoxyglucose 18FFDG These agents which reflect the physiological changes that are part of the inflammatory process are taken up directly by cells tissues and organs or are attached to native substances that subsequently migrate to an inflammatory focus Because they provide different types of information anatomical and molecular imaging studies are complementary to each another There are certain situations however in which molecular imaging tests are especially valuable postoperative infections and infections associated with orthopedic hardware notably prosthetic joint infection Postoperative infections are a significant cause of morbidity and mortality Ultrasound CT and magnetic resonance imaging MRI cannot consistently separate abscesses from other fluid collections and on occasion even from normal postoperative changes The distorted anatomy metallic sutures and the surgical incision itself further complicate study interpretation Molecular imaging studies however demonstrate physiological processes which often precede anatomical changes and can help distinguish normal postoperative inflammation from infection In suspected orthopedic hardware infection plain radiographs are neither sensitive nor specific and crosssectional imaging modalities such as CT and MRI are limited by hardwareinduced artifacts Radionuclide imaging is not affected by metallic hardware and is the current imaging modality of choice for diagnosing orthopedic hardware infectionThis article reviews the various radiolabeled molecular imaging agents used for detecting and localizing inflammation and infection as well as the potential role of these agents in guiding selection of therapeutic agents and monitoring treatment responseSeveral factors contribute to gallium67 citrate 67Gacitrate uptake in inflammation and infection About 90  of circulating Ga ions are bound to transferrin in the plasma Increased blood flow and vascular membrane permeability result in increased 67Ga delivery and accumulation at the inflammatory foci 67Ga also binds to lactoferrin which is present in high concentrations in inflammatory foci Direct bacterial uptake complexing with siderophores and leukocyte transport also contribute to 67Ga uptake in inflammation and infection Imaging usually is performed 18–72 h after injection The normal distribution of 67Ga which is variable includes bone marrow liver gastrointestinal and urinary tracts and soft tissues 1Replaced by labeled leukocyte imaging for most indications 67Ga remains useful in select circumstances Opportunistic infections affect the lungs and a normal scan of the chest excludes infection with a high degree of certainty In HIVpositive patients lymph node uptake is associated with mycobacterial infection and lymphoma Focal or localized pulmonary parenchymal uptake usually is associated with bacterial pneumonia Diffuse pulmonary uptake especially when intense suggests Pneumocystis jirovecii pneumonia 167Ga is a sensitive indicator of pulmonary inflammation and accumulates in interstitial pneumonitis drug reactions collagen vascular disease pneumoconioses and sarcoidosis In patients with sarcoidosis uptake correlates with disease activity and response to therapy 1

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