Lymphoma, melanoma, colon cancer: diagnosis and treatment with radiolabeled monoclonal antibodies. The 1986 Eugene P. Pendergrass New Horizons Lecture.
The development of monoclonal antibodies for use as in vivo carriers of radioactivity for diagnosis and therapy of malignant neoplasms is proceeding rapidly within academic and commercial sectors. The author and his colleagues studied anticancer antibodies formed against tumors of both somatic and hematopoietic origins. Several general principles have been established with the work with somatic tumors, including the following: Improved tumor-to-normal-tissue ratios can be achieved with Fab fragments as opposed to whole IgG; each antitumor antibody has a characteristic biodistribution in humans that cannot be readily predicted from tissue or small animal studies; and for many antibodies, there is a strong dependency of tumor uptake on total mass amount of antibody administered (greater uptake with greater mass dose). Initial work with iodine-131 labeled Fab fragments of the antimelanoma antibodies, 96.5 and 48-7, documented that tumor uptake was broadly proportional to antigen content of the tumors and that under optimal conditions, some tumors were sufficiently loaded with radiolabeled antibody to serve as radiation therapy. In one patient, an objective response was seen that lasted for 4 months; of five other patients, one had long-term stabilization of a previously rapidly growing tumor; two other patients had no response at doses of radioactivity that had caused significant bone marrow suppression but no treatment-related symptoms or morbidity. The antitumor antibody B-72.3, as IgG, has been particularly promising when administered intraperitoneally. In ten patients who were administered I-131 B-72.3 via a Tenkhoff catheter, the sensitivity and specificity of tumor location were excellent for peritoneal implants, and in three of these patients, surgically confirmed tumor was seen with the radiolabeled antibody technique when abdominal computed tomography and magnetic resonance studies were negative. In a separate series of 20 patients with mycoses fungoides, the anti-lymphoma antibody T-101 (recognizes the pan T-cell antigen, T-65), when labeled with indium-111, demonstrated lymph node involvement with greater sensitivity than conventional diagnostic methods and with excellent specificity. Radiolabeled antitumor B-72.3 and T-101 both show promise in antitumor therapy. Although much remains to be done on technical and biologic research levels before these radiopharmaceuticals can be routinely applied to all forms of cancer, these clinical research examples suggest that under proper conditions of use, radiolabeled monoclonal antibodies will have a major impact on the future practice of nuclear medicine.
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000951:Antigens, Neoplasm / Q000276:immunology; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy; D003947:Diagnostic Techniques, Radioisotope; D006801:Humans; D007205:Indium Radioisotopes / Q000008:administration & dosage; D007457:Iodine Radioisotopes; D008223:Lymphoma / Q000000981:diagnostic imaging*; D008545:Melanoma / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D011868:Radioisotopes / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D012878:Skin Neoplasms / Q000000981:diagnostic imaging; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D011868:Radioisotopes