Evaluation of the 323/A3 monoclonal antibody and the use of technetium-99m-labeled 323/A3 Fab' for the detection of pan adenocarcinoma.
The 323/A3 murine monoclonal antibody, initially described as reactive to breast carcinomas, is found by immunohistological analyses to have broad cross reactivity with adenocarcinomas of diverse histologic origin. The 323/A3 antigen is similar to the tumor-associated 17-1A antigen as revealed by immunoblot and cross-competition cell binding studies. We have investigated the potential use of the 323/A3 monoclonal antibody for tumor imaging as a Fab' molecule labeled with 99mTc. In vitro studies demonstrate that 323/A3 Fab' has high affinity (2-3 x 10(9) M-1) with no significant loss of immunoreactivity compared to the intact IgG. In vivo studies demonstrate that 99mTc 323/A3 Fab' can rapidly detect human breast and colon tumor xenografts growing in athymic nude mice. Distinct breast tumor visualization is observed as early as 1 h post intravenous administration with the 99mTc 323/A3 Fab'. Distinct colon tumor visualization is observed by 3 h (the earliest time point imaged). Tumor-to-blood ratios are higher for 99mTc 323/A3 Fab' than with a 99mTc-labeled nonspecific isotype-matched Fab' antibody. These results suggest that 99mTc 323/A3 Fab' can detect 17-1A antigen and may have potential clinical utility for the rapid diagnostic imaging of adenocarcinomas.
Research and Development Division, Centocor, Inc., Malvern, PA 19355.
K Y
KY
Pak
M A
MA
Nedelman
W E
WE
Fogler
S H
SH
Tam
E
E
Wilson
L J
LJ
Van Haarlem
R
R
Colognola
S O
SO
Warnaar
P E
PE
Daddona
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000276:immunology; D003110:Colonic Neoplasms / Q000276:immunology; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D006825:Hybridomas; D007140:Immunoglobulin Fab Fragments; D007150:Immunohistochemistry; D007553:Isotope Labeling; D051379:Mice; D008819:Mice, Nude; D010446:Peptide Fragments / Q000276:immunology; D013667:Technetium; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010446:Peptide Fragments; D013667:Technetium