Radiotracers used for the scintigraphic detection of infection and inflammation

Abstract

Over the last forty years, a small group of commercial radiopharmaceuticals have found their way into routine medical use, for the diagnostic imaging of patients with infection or inflammation. These molecular radiotracers usually participate in the immune response to an antigen, by tagging leukocytes or other molecules/cells that are endogenous to the process. Currently there is an advancing effort by researchers in the preclinical domain to design and develop new agents for this application. This review discusses radiopharmaceuticals used in the nuclear medicine clinic today, as well as those potential radiotracers that exploit an organism's defence mechanisms to an infectious or inflammatory event.

Figure 1

Schematic representation of an immune response to a bacterial infection. Tethering: P-selectins bind to PSGL-1 and tether PMN. Rolling: P-selectins bring PMN near E-selectins and slow rolling commences. Chemokine signalling: slow rolling allows IL-8 binding to CXCR1, then integrin activation results in more adhesive interactions with endothelial ligands. Adhesion: activated LFA-1 binds ICAM-1 or ICAM -2 for firm adhesion. Diapedesis: PMN begins diapedesis by exchanging tight junction molecules with endothelial cells. Migration: PMN follows a gradient of inflammatory chemokines to pathogens. Attack: complement attacks the incoming pathogens, mast cells, and macrophage phagocytose pathogens; toll-like receptor molecules trigger inflammation; antigen presenting dendritic cells express MHC molecules to activate T lymphocytes and to recruit neutrophils. PMN = polymorphonuclear neutrophil; CXCR/CCR = chemokine receptor; s-Le-x = sialyl-Lewis X; LFA = lymphocyte function-associated antigen; PSGL = P-selectin glycoprotein ligand; IL = interleukin; CD = cluster of differentiation; CD11a/CD18 = integrins; RBC = red blood cell; JAM = junctional adhesion molecule; PECAM = platelet endothelial cell adhesion molecule; DC = dendritic cell; MHC = major histocompatibility complex; T cell = T lymphocyte; IP-10 = interferon-gamma induced protein-10; MIP = macrophage inflammatory protein; RANTES = regulated on activation, normal T cell expressed and secreted (CCL5 chemokine); TNFα = tumor necrosis factor alpha; C3a and C5a = complement components 3a and 5a; LTB4 = leukotriene B4.

Figure 2

Four-hour whole body images of rats with a TNBS-colitis, injected with (a) ^99mTc-alafosfalin (annotated line represents the descending colon plus increased uptake ◂ in distal colon) and (b) ^99mTc-DTPA.

Figure 3

Anterior static images of a sheep taken at 24, 48, and 144 hours after a subcutaneously injected dose (id) of ¹¹¹In-dendritic cells in the neck and migration to the nearest lymph node (◂).

Figure 4

An annotated diagram of IgG depicting the antigen binding sites and isotope binding sites.

Figure 5

Whole body images of rats with S. aureus infections (◂) in left thigh at 4 hours pi with (a) ^99mTc-hIgG and (b) ^99mTc-rIgG.

Figure 6

Four-hour ^99mTc-infliximab distribution in a rat with TNBS-colitis: (a) whole body image (annotated line represents the descending colon, with increased uptake ◂ in distal colon); (b) resected intestine after TNBS exposure (distal inflammation); and (c) radiotracer distribution in the same resected specimen (R = rectum).