PRECLINICAL STUDIES OF INDIUM-111-LABELED IGM - A HUMAN MONOCLONAL-ANTIBODY FOR INFECTION IMAGING

Indium-111-labeled plasma proteins, such as albumin, transferrin and I gG, have been proven useful to image infection. We reported previously that In-111-labeled human monoclonal antibody, IgM 16.88 (In-IgM) als o would localize at the site of infection. However, the kinetics of bl ood clearance, distribution and infection uptake have not been investi gated. We compared the kinetics of distribution and infection uptake o f In-IgM 16.88 with that of In-polyclonal IgG in rats with focal infec tion. Methods: Both IgM 16.88 and polyclonal IgG were labeled with In- 111 using a bifunctional chelating agent, LiLo. The labeling efficienc y was >95%. Focal infection was induced in rats by an intramuscular in jection of E. Coli in the right thigh. In-IgM (30-40 mu Ci) was inject ed 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, inf ection muscle, control muscle, liver, spleen and kidney were determine d. Similar studies were performed with In-IgG. Results: The In-IgM act ivity 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, t he 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 comp ared to diffuse abdominal uptake of IgG. Conclusion: These results ind icate that In-IgM produces higher lesion to background ratio when comp ared to In-IgG and, therefore, is potentially useful to image infectio n in patients.