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 (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.
Blankenberg
F G
FG
Division of Pediatric Radiology, Lucile Salter Packard Children's Hospital, Stanford, Calif, USA. blankenb@leland.stanford.edu
Tait
J F
JF
Blankenberg
T A
TA
Post
A M
AM
Strauss
H W
HW
D000038:Abscess / Q000000981:diagnostic imaging* / Q000473:pathology; D000818:Animals; D017304:Annexin A5; D017209:Apoptosis; D001345:Autoradiography; D018932:Chemokine CCL2 / Q000493:pharmacokinetics; D002908:Chronic Disease; D006098:Granulocytes / Q000000981:diagnostic imaging*; D006614:Hindlimb; D008264:Macrophages / Q000000981:diagnostic imaging*; D008297:Male; D009000:Monocytes / Q000000981:diagnostic imaging; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012588:Scintillation Counting; D012710:Serum Albumin, Bovine; D012711:Serum Albumin, Radio-Iodinated; D013667:Technetium / Q000493:pharmacokinetics; D014018:Tissue Distribution
D017304:Annexin A5; D018932:Chemokine CCL2; D011994:Recombinant Proteins; D012711:Serum Albumin, Radio-Iodinated; D012710:Serum Albumin, Bovine; D013667:Technetium