Biodistribution and pharmacokinetic screening in humans of monoclonal antibody AR-3 as a possible immunoscintigraphy agent in patients with pancreatic cancer.
This pharmacokinetic study was performed in order to assess the potential usefulness of the murine monoclonal antibody (MoAb) AR-3-IgG1 as an immunoscintigraphy agent for pancreatic cancer. This MoAb, which defines a mucin-like antigen (CAR-3) expressed by a large fraction of pancreatic cancers, shows in fact favourable in vivo localizing properties in the experimental animal model of human tumor xenograft. 131I-AR-3-IgG1 was injected i.v. into 5 patients with suspected pancreatic cancer. Whole-body maps and spot views of the abdominal area were recorded with a computerized gamma-camera, and specific regions of interest drawn over the liver and spleen helped to define the kinetics of activity in these organs. Blood samples taken from 0.1-144 hours post-injection and daily urine collections over the same interval served to define the kinetics of plama distribution and removal of activity from the body. Different multicompartmental models were tested to fit the experimental data, assuming as the starting hypothesis that there was to be significant nonspecific tracer accumulation in the liver, spleen and bone marrow, as already observed for the majority of radioiodinated murine MoAbs injected into humans. Surgery confirmed pancreatic cancer in 3 out of the 5 patients (chronic pancreatitis and periampullary cancer in one each); in all these 3 patients immunostaining with the MoAb AR-3 demonstrated the presence of the CAR-3 antigen (with a cytoplasmic and endoluminal/secretory pattern of distribution). Nonspecific radioactivity accumulation in the liver, spleen and bone marrow was extremely low, linked essentially to the blood pool effect of circulating activity in these organs.(ABSTRACT TRUNCATED AT 250 WORDS)
Mariani
G
G
CNR Institute of Clinical Physiology, University of Pisa, Italy.
Molen
N
N
Bacciardi
D
D
Boggi
U
U
Bonino
C
C
Costa
A
A
Viacava
P
P
Castagna
M
M
Bodei
L
L
Tarditi
L
L
D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D014408:Biomarkers, Tumor / Q000276:immunology; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging*; D010865:Pilot Projects; D016719:Radioimmunodetection; D014018:Tissue Distribution; D000951:Antigens, Neoplasm
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D007457:Iodine Radioisotopes; C068379:CAR-3 antigen; D000951:Antigens, Neoplasm