Imaging macrophages and the apoptosis of granulocytes in a rodent model ofsubacute and chronic abscesses with radiolabeled monocyte chemotactic peptide-1 and annexin V

Monocytes/macrophages (Mos), the predominant cell types in subacute and chr onic inflammation, are attracted to and activated by monocyte chemotactic p eptide-1 (MCP-1). Mos promote the resolution of inflammation through the in duction of apoptosis and phagocytosis of senescent (spent) and bystander (s uperfluous) granulocytes. We wished to determine whether MCP-1, which selec tively binds to Mos, could be used to image subacute and chronic inflammati on. We also sought to image granulocyte apoptosis within these lesions with technetium-99m labeled annexin V, a marker of apoptotic cells. Sterile inf lammation was induced in 45 12-week-old male Sprague-Dawley rats by deep in tramuscular injection of turpentine into the right thigh. Groups of four to six animals were then imaged I h after tail vein injection of 37-148 MBq ( 1-4 mCi) of Tc-99m-labeled MCP-I or annexin V 1-14 days after turpentine tr eatment. Image analysis showed significantly greater activity of both MCP-I and annexin V in inflamed thighs than in control thighs (165%-290% and 188 %-313%, respectively; P <0.01) on days 1-5 after turpentine injection. Dual autoradiography in animals co-injected with iodine-125 labeled bovine seru m albumin on days I and 4 showed specific location of MCP-1 to infiltrating Mos while annexin V localized to focal zones of apoptosis within granulocy tic infiltrates adjacent to abscess cavities. Scintillation well counting o n day 5 demonstrated significantly higher (P <0.005) ratios of abscess to c ontrol thigh specific activities for MCPA (5.83 +/-2.17) and annexin V (9.2 4 +/-2.8) as compared to I-125-labeled bovine ser-um albumin (3.11 +/-0.65) . No significant increases in uptake were noted at imaging or ex vivo analy ses on days 13 and 14, when lesions were predominately fibrotic. It is conc luded that Tc-99m-labeled MCP-1 and Tc-99m-labeled annexin V both localize in zones of subacute inflammation, reflecting the density of Mos and the in cidence of apoptotic granulocytes, respectively. These agents may be useful in the characterization of subacute inflammation.