Reduction of background activities by introduction of a diester linkage between antibody and a chelate in radioimmunodetection of tumor.
A diester linkage was added between monoclonal anti-melanoma antibody 96.5 and a diethylenetriaminepentaacetic acid derivative to test if a tumor-to-blood and -to-organ ratio of the injected antibody in nude mice with human melanoma FEM XII xenografts could be increased by the addition of the readily cleavable linkage. Compared to the 111In-labeled antibody DTPA with a peptide linkage, the diester conjugate cleared much faster from the blood and was retained much less in muscle and normal organs such as liver, spleen and kidney over a 48-hr period. On the other hand, the activity retained in the tumor was larger than or similar to that of the peptide conjugate for this time period. This resulted in a 2.5, 2.1, and 2.6 fold increase in a tumor to blood, to liver and to kidney ratio at 48 hr for the diester conjugate as compared to the peptide conjugate. The whole-body biologic half life of the antibody was 36 hr, three times shorter than the peptide conjugate. The external imaging demonstrated a clearly visible tumor at 4 hr and a lower pool activity at 72 hr for the diester conjugate. The peptide conjugate, however, showed a persistant blood-pool activity at 72 hr. The addition of the diester linkage, therefore may be beneficial for imaging tumors in patients at early time intervals after injection.
Paik
C H
CH
Radiopharmaceutical Chemistry Section, George Washington University Medical Center, Washington, DC.
Yokoyama
K
K
Reynolds
J C
JC
Quadri
S M
SM
Min
C Y
CY
Shin
S Y
SY
Maloney
P J
PJ
Larson
S M
SM
Reba
R C
RC
D000818:Animals; D000911:Antibodies, Monoclonal; D001667:Binding, Competitive; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging*; D051379:Mice; D008819:Mice, Nude; D004369:Pentetic Acid / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D004369:Pentetic Acid