Kinetics and tissue distribution of the radiolabeled chimeric monoclonal antibody MOv18 IgG and F(ab')2 fragments in ovarian carcinoma patients.
Twenty-four patients suspected of having ovarian carcinoma received i.v. injection with a combination of radiolabeled intact IgG (1 mg) and F(ab')2 fragments (1 mg) of the chimeric monoclonal antibody MOv18, each form labeled with 1.85 MBq 131I or 125I. Laparotomy was performed either 2 or 6 days after injection, and the uptake of radioactivity was determined in a total of 329 biopsies of normal and malignant tissues. The mean elimination half life in plasma of cMOv18 IgG and F(ab')2 was 70 +/- 8 (SD) and 20 +/- 5 h, respectively. The mean uptake of IgG in tumor biopsies was 3.6-fold higher two days after injection and 6.9-fold higher than the uptake of F(ab')2 6 days after injection. Uptake in normal tissues was 3.3 and 5.5 times higher for IgG at 2 and 6 days, respectively. Two days after injection, the mean ratio of the uptake in tumor:normal tissue/patient was 3.8 +/- 1.5 and 4.0 +/- 1.8 for radiolabeled cMOv18 IgG and F(ab')2, respectively. Six days after injection, this was 6.7 +/- 4.7 for Ig G and 5.7 +/- 4.1 for F(ab')2. cMOv18 IgG has a longer circulation time in blood, a higher uptake in tumor and normal tissues, and a longer retention time compared to the F(ab')2 fragments. However, the tumor:normal tissue ratios are similar. The results do not warrant a definite conclusion as to which antibody form is most suitable for therapeutic application of antibodies but provide a more firm basis for rational design of therapeutic targeting studies using immunoconjugates.
Buist
M R
MR
Department of Obstetrics and Gynecology, Free University Hospital, Amsterdam, The Netherlands.
Kenemans
P
P
den Hollander
W
W
Vermorken
J B
JB
Molthoff
C J
CJ
Burger
C W
CW
Helmerhorst
T J
TJ
Baak
J P
JP
Roos
J C
JC
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000378:metabolism; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins