Radioimmunology. Imaging and therapy

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Abstract
Targeting of radioactivity to tumors using antitumor antibodies is evolving from a laboratory curiosity toward a practical diagnostic and therapeutic technique that promises widespread benefits for many common human cancers. The development of the hybridoma technique by Kohler and Milstein for producing monoclonal antibodies is probably the single most important contribution to the development of this field. A large array of monoclonal antibodies against many human tumors have been created and labeled with a variety of radioisotopes; 110 clinical trials have been identified from the literature between the interval of 1978 to the present. These studies are beginning to form the basis for certain conclusions regarding likely benefits for certain combinations of antitumor antibodies and isotopes in specific instances of clinical management in patients with malignant neoplasms. For example, in melanoma, lymphoma, neuroblastoma, and colorectal malignancies, radiolabeled antibodies have demonstrated occult tumors, which could not be disclosed with conventional methodologies. Radioimmunotherapy of malignant lymphoma is achieving durable remissions in patients who have failed conventional forms of therapy. For the most part, these advances have been achieved through intelligent application of known principles of immunochemistry, imaging physics, and tumor immunology. Progress has been slow but steady. In a few instances, the term "magic bullet" is warranted in describing the targeting of a particular radiolabeled antibody to a human tumor. I-131, 3-F8, an IgG3 against the GD2 antigen of neuroblastoma, which was introduced by Cheung, and In-111 T-101, against the CD5 antigen of T-cells, which was developed by Royston, stand out because of the consistency and high concentration of radioactive targeting to human tumors in clinical trials. If certain technical innovations fulfill their initial promise, the future will be bright for radioimmunologic methods of diagnosis and therapy. Genetic engineering will permit the development of "humanized" antibodies with biologic properties that favor tumor localization. New chemical approaches will broaden the range of isotopes available as diagnostic and therapeutic radiolabels. Application of modern imaging methodologies, such as positron emission tomography (PET), will detect more lesions of smaller size and permit quantitative imaging for dosimetry considerations. Greater speed and ease of use of computerized work stations will lead to the broader application of fusion imaging in which radioantibody images will be viewed simultaneously with TCT or MRI for better anatomic correlation of abnormal sites of antigen-reactive tumor deposits.