Biodistribution of 111In-labelled IgG and IgM in experimental infection.
Both the protein used and the conjugation method are factors which may be relevant for targeting infection with 111In-labelled proteins. In this study, human immunoglobulin G (IgG), conjugated to either DTPA or LiLo, and LiLo conjugated human immunoglobulin M (IgM) were evaluated. In rats with Staphylococcus aureus calf muscle infection, biodistribution was determined 6, 24 and 48 h after the injection of 111In-DTPA-IgG, 111InLiLo-IgG or 111In-LiLo-IgM. Absolute abscess uptake of 111In-LiLo-IgG was significantly higher than that of 111In-DTPA-IgG (P < 0.05). Since blood clearance of 111In-LiLo-IgG was initially significantly slower (P < 0.01), the higher abscess uptake did not result in higher abscess-to-background ratios. 111In-LiLo-IgG accumulated to a greater extent in the liver (P < 0.001). 111In-DTPA-IgG showed higher uptake in the kidneys and bone marrow (P < 0.001 and P < 0.01, respectively). Although decreasing over time, 111In-LiLo-IgM showed reasonable abscess uptake and rapid blood clearance, resulting in higher abscess-to-background ratios compared with 111In-LiLo-IgG (P < 0.01). However, liver and spleen uptake were three- to four-fold higher than that of 111In-LiLo-IgG (P < 0.001). Compared with DTPA-conjugation, chelation with LiLo has a minor influence on abscess targeting of 111In-labelled IgG. However, differences in blood clearance and organ uptake do occur. 111In-LiLo-IgM shows high relative accumulation in abscesses as well as high liver and spleen uptake. 111In-LiLo-IgM appears promising for imaging infection outside the trunk region.
Oyen
W J
WJ
Department of Nuclear Medicine, University Hospital Nijmegen, The Netherlands.
Boerman
O C
OC
Subramanian
R
R
Koenders
E B
EB
Claessens
R A
RA
van der Meer
J W
JW
Corstens
F H
FH
D000818:Animals; D002614:Chelating Agents / Q000493:pharmacokinetics; D004355:Drug Stability; D005069:Evaluation Studies as Topic; D006801:Humans; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D004369:Pentetic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000000981:diagnostic imaging* / Q000276:immunology / Q000378:metabolism; D014018:Tissue Distribution
D002614:Chelating Agents; C069971:DTPA-IgG complex; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007205:Indium Radioisotopes; C076593:1,3-bis(N-(N-(2-aminoethyl)-2-aminoethyl)-2-aminoacetamido)-2-(4-isothiocyanatobenzyl)propane-N,N,N',N'',N''',N'''',N''''',N'''''-octaaceticacid; D004369:Pentetic Acid