Initial tumor targeting, biodistribution, and pharmacokinetic evaluation of the monoclonal antibody PAM4 in patients with pancreatic cancer.
This pharmacokinetic study was performed to assess the potential usefulness of the murine monoclonal antibody (MoAb) PAM4-IgG1 as an immunotargeting agent for pancreatic cancer imaging or therapy. This MoAb reacts specifically with mucin purified from human pancreatic cancer. 131I-labeled PAM4-IgG1 was injected i.v. into five patients with suspected pancreatic cancer. Whole-body scans and spot views of the abdominal area were recorded with a computerized gamma camera, and specific regions of interest were drawn over the liver and spleen to define the kinetics of activity in these organs. Blood samples taken from 0.1-144 h after injection served to define the kinetics of plasma distribution and removal of activity from the body. Surgery confirmed pancreatic cancer in four of the five patients, whereas chronic pancreatitis was present in the fifth patient; in all four pancreatic cancer patients, 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 of scintigraphic maps recorded over the abdomen was quite satisfactory due to the low liver and spleen activity, with good scintigraphic demonstration of the pancreatic cancers (either primary or metastatic); the 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 tumor lesions was usually late, starting at about 72-96 h after tracer injection. The results obtained in this preliminary study indicate the potential usefulness of MoAb PAM4 for immunoscintigraphy in patients with either primary and/or recurrent pancreatic cancer while also suggesting that the use of the faster-clearing Fab fragments of this MoAb probably would result in improved immunoscintigraphic properties.
D000368:Aged; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D016719:Radioimmunodetection; D016499:Radioimmunotherapy; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes