Distribution of 111In- and 125I-labeled monoclonal antibody 17-1A in mice bearing xenografts of human pancreatic carcinoma HuP-T4.
BACKGROUND
The prognosis of pancreatic adenocarcinoma still remains poor because of the lack of reliable diagnostic tests for early stages of the disease. Monoclonal antibody 17-1A (MoAb 17-1A) has been studied extensively, and the antigen recognized by MoAb 17-1A is expressed by adenocarcinomas of the pancreas and stomach, as well as other normal and malignant epithelial tissues. The potential of MoAb 17-1A was investigated for its ability to detect pancreatic carcinomas. The use of MoAb 17-1A in treatment also was studied.


METHODS
Immunoreactivity of MoAb 17-1A with human pancreatic carcinoma cell line HuP-T4 was examined histochemically by the avidin-biotinylated enzyme complex method. MoAb 17-1A was labeled with 125I by the Iodogen method and 111In using either diethylenetriaminepentaacetic anhydride (cDTPA) or 1-(p-benzyldiazonium) diethylenetriaminepentaacetic acid (aDTPA). After injection in nude mice bearing HuP-T4 xenografts, the biodistribution of 111In- and 125I-labeled MoAb 17-1A was examined at various time points.


RESULTS
Positive staining of MoAb 17-1A was noted for HuP-T4 cells. A statistically significant (P < 0.01) greater tumor uptake was observed at 3 days after intravenous injection of 125I-labeled MoAb 17-1A when compared with 125I-labeled nonspecific immunoglobulin G. 125I- and 111In-labeled MoAb 17-1A was concentrated in HuP-T4 carcinoma 1.9-4.8 times higher than in the spleen, heart, liver, and pancreas.


CONCLUSIONS
MoAb 17-1A was found to bind selectively to human pancreatic carcinoma HuP-T4. Tumor exhibited higher uptake of radiolabeled MoAb 17-1A compared with adjacent normal tissues. These results suggest that MoAb 17-1A may be applicable to the radioimmunodetection and radioimmunotherapy of pancreatic adenocarcinomas.
Maeda
M
M
Department of Radiological Sciences, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Shoji
M
M
Kawagoshi
T
T
Futatsuya
R
R
Honda
T
T
Brady
L W
LW
D000042:Absorption; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D006801:Humans; D000922:Immunotoxins / Q000378:metabolism*; D007205:Indium Radioisotopes / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes