The use of
antibodies directed against
tumors has found increasing usefulness after the discovery by Kohler and Milstein of hybridoma technology, which made it possible to obtain
monoclonal antibody (MoAb) that reacted specifically against a particular
epitope on a particular
antigen site. Relative
tumor specificity and a lack of significant toxicity, together with the ability to link
radionuclides (both
halogens and metals) without significant deterioration of
biologic behavioral characteristics such as immunoreactivity, have enabled widespread use of radiolabeled MoAbs in several
malignancies, including and especially
malignant melanoma. There is a significant body of data indicating that radiolabeled MoAbs directed against
melanoma-associated
antigens have an important role in the detection and
therapy of metastatic
malignant melanoma. Detection of visceral disease, while currently suboptimal, will in the future improve with optimization of SPECT imaging using 99mTc-labeled MoAb
Fab fragments. This may result in an attenuated or absent antimouse response, especially after one injection, unless of course coinfused with either specific and/or nonspecific intact
immunoglobulin (Ig). Radiolabeled fragments play an important role in
radioimmunotherapy in metastatic
melanoma. This role may be enhanced by the development of newer
chelating agents that will decrease nonspecific hepatic uptake of
radionuclide, enabling the use of beta-emitting radiometals such as 90Y. The recent report demonstrating diminished hepatic uptake of 99mTc-labeled anti-high molecular weight
antigen (HMWA) Fab shows promise, since the same labeling technique can be used to deliver radiotherapeutic agents such as 186Re, which may be labeled to MoAb with methods similar to those used for 99mTc. Creation of single-chain MoAb determinants, chimera, and human MoAb will obviate the human immune response to foreign
proteins that are currently in use and enable multiple administrations of
tumor-toxic quantities of radiolabeled MoAbs.