Radiopharmaceuticals for Therapy by F. F. (Russ) Knapp & Ashutosh Dash

Author:F. F. (Russ) Knapp & Ashutosh Dash
Language: eng
Format: epub
Publisher: Springer India, New Delhi

There are several instances when RIT is extremely valuable (Sautter-Bihl et al. 1996) and include residual micrometastatic lesions, residual tumor margins after surgical resection, tumors in the circulating blood including hematologic malignancy, and malignancies that present as free-floating cells.

9.6.2 Selection of Target Antigen

The choice of the target antigen plays a key role in determining the success of RIT. The antigen should be confined to the malignant cells for effective targeting and prevent a subpopulation of antigen-negative cells from proliferating, and for this reason, a favorable antigen expression profile is desirable for successful tumor targeting. To ensure specificity, the antigen must be overexpressed in target cells and have minimum presence in healthy cells. In terms of antigen location and binding stability, effective antibody-mediated cytotoxicity is achieved if the target antigen is not internalized or shed following antibody binding. In order to achieve effective therapy, a high density of antibody binding to the cell surface is essential, and of course antigens that shed from the cell surface and circulate in the peripheral blood at high concentration are not useful targets in these cases. Finally, the chosen antigen should not mutate in a way that would allow cancer cells to avoid destruction by the immune system. Based on the above criteria, a wide variety of antigens on cell surface have been considered as targets for a variety of tumors which fulfill such criteria to differing degrees (Caron et al. 1994; Goldenberg et al. 1981; Schlom et al. 1990) (Fig. 9.7).

Fig. 9.7Illustration of the expression of multiple cell surface epitopes

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