Pharmacology

The radiolabeled MoAbs consist of a MoAb coupled with a radionuclide. This therapeutic modality was developed to act as a "guided missle"; the MoAb delivers ionizing radiation solely to cells that express the antigenic determinant to which the antibody was originally developed. Thus, healthy cells are spared from the toxic effects of the radiation. Hematologic malignancies are ideal candidates for this type of treatment because they are known to be exquisitely radiosensitive.543 Radiolabeled MoAbs offer certain advantages over other MoAbs: They do not depend on host effector mechanisms or cellular internalization transport mechanisms to exert their toxic effects; rather, they emit continuous, decreasing, low-dose-rate irradiation in the form of electrons, or p~ particles, that are discharged over 1-5 mm.43 These particles induce lethal DNA damage to antigen-positive cells as well as neighboring cells in close proximity to target cells.5 44 This can be advantageous when treating physically inaccessible, bulky tumors. Two major radionuclides are currently used in radioimmunoconjugate synthesis: 131I and 90Y. These two radionuclides differ slightly in terms of radiation and half-life. 131I emits not only p~ particles, but also a high degree of y radiation. The half-life of 131I is 193 h. In contrast, 90Y emits only 0" particles and has a much shorter half-life of 64 h.5 However, 90Y emits higher energy particles that actually penetrate deeper into tissue. Theoretically, this may be advantageous when treating larger, more bulky tumors. On the other hand, 90Y is less readily available and more expensive than 131I. In addition to the DNA damage induced by the radionuclide, there is some evidence to suggest that the antibody itself stimulates host immune effector mechanisms, which may account for some of the activity of these radioim-munoconjugates in non-Hodgkin's lymphoma.44

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