Comparative study of intact A7 MoAb and F(ab')2 fragments for radioimmunoimaging of human colon cancer in nude mice.
Differences of pharmacokinetics and tumor imaging ability between intact monoclonal antibody A7 (A7 MoAb) and F(ab')2 fragments were studied in human colon cancer (LS-174T)-bearing nude mouse. First of all, we examined the yield and the immunoreactivity of F(ab')2 fragments after treatment with ficin as a function of time. The yield of F(ab')2 fragments reached about 50% after ficin treatment for 8 h, and the F(ab')2 retained about 80% of the immunoreactivity of the corresponding MoAb. Longer digestion with ficin produced smaller fragments (less than 92 kDa) with a lower yield and most of the immunoreactivity was lost. In pharmacokinetics studies, the F(ab')2 was preferentially taken up by the tumor, was cleared more rapidly from the blood circulation and seemed to have less non-specific tissue binding than intact A7 MoAb. In addition, the tumor image obtained at an early time using 131I-F(ab')2 was much superior in quality to that with intact 131I-A7 MoAb. The use of F(ab')2 fragments may be effective for tumor diagnosis and therapy.
Kojima
S
S
Research Institute for Biosciences, Science University of Tokyo, Chiba, Japan.
Suzuki
N
N
Shimura
N
N
Kubodera
A
A
Kubota
K
K
Yamaguchi
T
T
Takahashi
T
T
Oyamada
H
H
D000818:Animals; D000911:Antibodies, Monoclonal; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging*; D005260:Female; D005361:Ficain / Q000737:chemistry; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016719:Radioimmunodetection / Q000379:methods*; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D005361:Ficain