[Subcellular kinetics of In-111 monoclonal antibody in the liver].
To evaluate the mechanism for prolonged retention of In-111 monoclonal antibody (MoAb) by the liver, we investigated the subcellular kinetics of the In-111 225.28S, an antimelanoma IgG2a. Forty microCi/10 micrograms of the In-111 MoAb was injected IV into groups of SD rats. The liver was excised at 3, 8, 17, 24, 48 and 72 hr and homogenized with 0.25 M sucrose containing 0.01 M Tris-HCl buffer (pH 7.6). Subcellular fractionation was carried out by 3-step (ultra-)centrifugation. The radioactivity of each fraction including nuclear, mitochondrial (lysosomal), microsomal and supernatant fraction was measured and expressed as a percentage of the total radioactivity of all the fractions. Moreover, the supernatant fraction was assessed by size exclusion HPLC. The supernatant was a predominant fraction of the In-111 radioactivity, 61% at 3 hr, and was decreased with time, 21% at 72 hr (p less than 0.01), while the activity in the mitochondrial fraction continued to increase from 11% to 44%. As compared to these two fractions, the nuclear and microsomal radioactivities were relatively constant, 10-25%, throughout the study. The HPLC analysis revealed that the supernatant In-111 activity at early time points was mainly eluted with an intact IgG and thereafter this major peak activity was reduced with associated activity peaks found in smaller moiety fractions. To compare the In-111 MoAb with the iodine labeled MoAb, we also investigated the subcellular kinetics of the I-125 MoAb in the same manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Kinuya
S
S
Yokoyama
K
K
Watanabe
N
N
Ureshino
T
T
Aburano
T
T
Tonami
N
N
Hisada
K
K
D000818:Animals; D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D007700:Kinetics; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D011877:Radionuclide Imaging; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes