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.