Abstract.
Monocytes/macrophages (Mφs), the predominant cell types in subacute and chronic inflammation, are attracted to and activated by monocyte chemotactic peptide-1 (MCP-1). Mφs 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 Mφs, 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 1 h after tail vein injection of 37–148 MBq (1–4 mCi) of 99mTc-labeled MCP-1 or annexin V 1–14 days after turpentine treatment. Image analysis showed significantly greater activity of both MCP-1 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 1 and 4 showed specific location of MCP-1 to infiltrating Mφs 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 MCP-1 (5.83±2.17) and annexin V (9.24±2.8) as compared to 125I-labeled bovine serum 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 99mTc-labeled MCP-1 and 99mTc-labeled annexin V both localize in zones of subacute inflammation, reflecting the density of Mφs and the incidence of apoptotic granulocytes, respectively. These agents may be useful in the characterization of subacute inflammation.
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Received 28 January and in revised form 28 April 2001
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Blankenberg, F.G., Tait, J.F., Blankenberg, T.A. et al. 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. Eur J Nucl Med 28, 1384–1393 (2001). https://doi.org/10.1007/s002590100572
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DOI: https://doi.org/10.1007/s002590100572