Monocytes/macrophages (Mphis), the predominant cell types in subacute and 
chronic inflammation, are attracted to and activated by monocyte chemotactic 
peptide-1 (MCP-1). Mphis 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 Mphis, 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 Mphis 
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 Mphis and the incidence of apoptotic 
granulocytes, respectively. These agents may be useful in the characterization 
of subacute inflammation.