Preclinical studies of indium-111-labeled IgM: a human monoclonal antibody for infection imaging.
Indium-111-labeled plasma proteins, such as albumin, transferrin and IgG, have been proven useful to image infection. We reported previously that 111In-labeled human monoclonal antibody, IgM 16.88 (In-IgM) also would localize at the site of infection. However, the kinetics of blood clearance, distribution and infection uptake have not been investigated. We compared the kinetics of distribution and infection uptake of In-IgM 16.88 with that of in-polyclonal IgG in rats with focal infection.


METHODS
Both IgM 16.88 and polyclonal IgG were labeled with 111In using a bifunctional chelating agent, LiLo. The labeling efficiency was > 95%. Focal infection was induced in rats by an intramuscular injection of E. Coli in the right thigh. In-IgM (30-40 microCi) was injected into five groups of rats (five rats/group). The rats were killed at 4, 8, 16, 24 and 36 hr. The percent injected dose (%ID) in blood, infection muscle, control muscle, liver, spleen and kidney were determined. Similar studies were performed with In-IgG.


RESULTS
The In-IgM activity in blood at 4 hr postinjection was 27% which decreased to 2% by 36 hr. In contrast, the In-IgG blood activity was 40% at 4 hr and 20% at 36 hr. The infection/ muscle (I/M) ratios are higher with In-IgM at all time points postinjection compared to that of In-IgG. At 24 hr, the I/M ratio was 22 compared to 9 with In-IgG. At the same time point, the infection/ blood (I/B) ratio with In-IgM was 2.7 compared to only 0.8 with that of In-IgG. In-IgM was taken up mostly by the liver compared to diffuse abdominal uptake of IgG.


CONCLUSIONS
These result indicate that In-IgM produces higher lesion to background ratio when compared to In-IgG and, therefore, is potentially useful to image infection in patients.
Subramanian
R
R
PerImmune, Inc., Rockville, Maryland 20850, USA.
Vallabhajoshula
S
S
Lipszyc
H
H
Zhao
Q
Q
Murray
J
J
Shaban
S
S
Machac
J
J
Hanna
M G
MG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D002614:Chelating Agents; D005260:Female; D005455:Fluorescent Antibody Technique; D005490:Focal Infection / Q000000981:diagnostic imaging* / Q000378:metabolism; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology*; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D004369:Pentetic Acid / Q000031:analogs & derivatives; D016719:Radioimmunodetection; D051381:Rats; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D002614:Chelating Agents; 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