Rapid background reduction of circulating sodium iodide I 125-labelled Pisum sativum agglutinin used as a tumor-imaging radiopharmaceutical by the chemically galactosylated antibody.
Influence on the clearance of background radioactivity from the blood was studied by using a chemically galactosylated antibody to the radiopharmaceutical. Sodium iodide I 125-labelled Pisum sativum agglutinin (125I-PSA) was used as the model tumor-imaging radiopharmaceutical in this series of experiments. Rabbit (anti-PSA) immunoglobulin G (IgG) was chemically galactosylated with varying amounts of cyanomethylgalactose. Galactose concentration ranged from 11 to 17 mol/mol protein. Antibody activity was not affected by chemical galactosylation under the experimental conditions used. Blood clearance of the galactosylated anti-PSA (GAP) in normal mice was enhanced to varying degrees, depending on the degree of galactosylation; similarly, liver uptake was increased with the degree of galactosylation. Following injection of 125I-PSA in normal mice, the lectin was rapidly removed from the blood by subsequent injection of GAP. Increased hepatic uptake of the complex (lectin-galactosylated antibody) via protein-carbohydrate recognition caused the pronounced decrease in the 125I-PSA blood level. The effective time for 125I-PSA removal was as short as 15 min. The potency was dependent on the degree of galactosylation of the antibody. In sarcoma 180 (S-180) tumor-bearing mice, the capacity for blood clearance of 125I-PSA was also positively correlated to the degree of galactosylation. Moreover, the variation in the delivered dose ratio of antibody to lectin proved to lead to a further increase in background clearance. As a result, especially the tumor:blood ratio was significantly improved by a single administration of chemically galactosylated antibody, as compared with the value measured in the presence of unmodified antibody. These initial studies suggest that administration of GAP may improve nuclear imaging with radiopharmaceuticals.
Research Institute for Biosciences, Science University of Tokyo, Chiba, Japan.
S
S
Kojima
K
K
Kubota
A
A
Kubodera
M
M
Imagawa
H J
HJ
Gabius
D000818:Animals; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D037102:Lectins / Q000276:immunology; D008756:Methylgalactosides / Q000378:metabolism; D051379:Mice; D037121:Plant Lectins; D011817:Rabbits; D011877:Radionuclide Imaging; D012510:Sarcoma 180 / Q000000981:diagnostic imaging*; D012974:Sodium Iodide
D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D037102:Lectins; D008756:Methylgalactosides; D037121:Plant Lectins; C036292:pea lectin; D012974:Sodium Iodide