PRECLINICAL ANALYSIS OF INTRAPERITONEAL ADMINISTRATION OF IN-111-LABELED HUMAN TUMOR REACTIVE MONOCLONAL IGM AC6C3-2B12

An IgM lambda human tumor cell-reactive monoclonal antibody was develo ped that reacts with cells of ovarian cancer, colorectal cancer, breas t cancer, and certain other malignancies, The monoclonal antibody AC6C 3-2B12, which was obtained from a recent recloning, was purified from tissue culture supernatants and analyzed by high-performance liquid ch romatography and sodium dodecyl sulfate-PAGE, An animal model was deve loped in which human tumors grew either as solid peritoneal metastases or as s,c, nodules utilizing the human colorectal carcinoma cell line SW620. The biodistribution of In-111-labeled IgM conjugate was studie d after i,v, or i,p, administration in nude mice bearing an s,c, xenog raft or peritoneal tumor lumps of a human colorectal carcinoma (SW620) , IgM administered i,v, cleared rapidly from blood and was deposited m ainly in the liver [50% injected dose/g (ID/g)], pancreas (20% ID/g), and kidney (10% ID/g) at 24 h, Tumor deposition was low (less than or equal to 1,0% ID/g) in the s,c. tumor xenograft, In contrast, high tum or targeting (29% ID/g) was found in peritoneal tumor lumps after i,p, administration of In-111-labeled IgM. The biological half-life of IgM in the tumor was 100 h, Long peritoneal residence time (t(1/2) = 67 h ) and low liver uptake (7% ID/g) were observed after i,p, administrati on, Blood activity was <1% of the injected activity, Tumor:normal orga n ratios were high (range, 2-290) from 2 to 144 h after i,p, administr ation, Whole body autoradiograms at 24 h after i.p. In-111-labeled IgM administration confirmed the biodistribution results, In normal beagl e dogs, 75% of the i,p,-administered In-111-IgM decayed in the periton eal cavity, The majority of the remaining radioactivity was taken up b y mediastinal lymph nodes, Biological half-life in both locations was approximately 137 h, The i,p, administration of intact, specific radio labeled IgM provides prolonged retention of radioactivity in tumor, lo w normal tissue uptake, a long peritoneal residence time, and very lim ited spillover of IgM into the circulation, This approach offers a pro mising new method for the diagnosis and treatment of certain patients with peritoneal carcinomatosis.