INITIAL TURNER TARGETING, BIODISTRIBUTION, AND PHARMACOKINETIC EVALUATION OF THE MONOCLONAL-ANTIBODY PAM4 IN PATIENTS WITH PANCREATIC-CANCER

This pharmacokinetic study was performed to assess the potential usefu lness of tile murine monoclonal antibody (MoAb) PAM4-IgG(1) as an immu notargeting agent for pancreatic cancer imaging or therapy, This MoAb reacts specifically with mucin purified from human pancreatic cancer. I-131-labeled PAM4-IgG(1) was injected i.v. into five patients with su spected pancreatic cancer, Whole-body scans and spot views of the abdo minal area were recorded with a computerized gamma camera, and specifi c regions of interest were drawn over the liver and spleen to define t he kinetics of activity in these organs, Blood samples taken from 0.1- 144 h after injection served to define the kinetics of plasma distribu tion and removal of activity from the body. Surgery confirmed pancreat ic cancer in four of the five patients, whereas chronic pancreatitis w as present in the fifth patient; in all four pancreatic cancer patient s, immunostaining with the MoAb PAM4 demonstrated the presence of the specific antigen, with a cytoplasmic and endoluminal/secretory pattern of distribution. Nonspecific radioactivity accumulation in the liver, spleen, and bone marrow was low, linked essentially to the blood pool effect of circulating activity in these organs, The overall quality o f scintigraphic maps recorded over the abdomen was quite satisfactory due to the low liver and spleen activity, with good scintigraphic demo nstration of the pancreatic cancers (either primary or metastatic); th e patient subsequently found to have pancreatitis failed to show PAM4 targeting, Except in one patient with widespread peritoneal metastases (in whom these tumor implants were detected scintigraphically already 24-48 hours after tracer injection), scintigraphic evidence of the tu mor lesions was usually late, starting at about 72-96 h after tracer i njection. The results obtained in this preliminary study indicate the potential usefulness of MoAb PAM4 for immunoscintigraphy in patients w ith either primary and/or recurrent pancreatic cancer while also sugge sting that the use of the faster-clearing Fah fragments of this MoAb p robably would result in improved immunoscintigraphic properties.