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

Monocytes/macrophages (Mos), the predominant cell types in subacute and chronic inflammation, are attracted to and activated by monocyte chemotactic peptide-1 (MCP-1). Mos promote the resolution of inflammation through the induction of apoptosis and phagocytosis of senescent (spent) and bystander (superfluous) granulocytes. We wished to determine whether MCP-1, which selectively binds to Mos, could be used to image subacute and chronic inflammation. We also sought to image granulocyte apoptosis within these lesions with technetium-99m labeled annexin V, a marker of apoptotic cells. Sterile inflammation was induced in 45 12-week-old male Sprague-Dawley rats by deep intramuscular 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 treatment. 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 serum 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 granulocytic infiltrates adjacent to abscess cavities. Scintillation well counting on day 5 demonstrated significantly higher (P <0.005) ratios of abscess to control thigh specific activities for MCPA (5.83 +/-2.17) and annexin V (9.24 +/-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 analyses on days 13 and 14, when lesions were predominately fibrotic. It is concluded 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 incidence of apoptotic granulocytes, respectively. These agents may be useful in the characterization of subacute inflammation.